Clarity Normal synovial \202 uid is clear and print can be read through it. As the cell c ount increases the \202 uid becomes progres- sively more opaque. Lipid crystals may be seen as Maltese cross-shaped deposits. Cytocentrifuge preparation Detailed cell analysis must be performed on a cytocentri- fuge p reparation. Neutrophils account for 60 \200\22380% of cells in in \202 ammatory arthritide s. In septic arthritis neutrophil counts may be 95% of nucleated cells present. Macro- phag es are predominant in viral arthritis. Viscosity Normal synovial \202 uid is viscous because it contains com- plex sugars. In in \202 ammatory disease there is enzymatic breakdown of these sugars and consequent fall in viscosity. Table 2.3 Feature of synovial \202 uid crystals Size (mm) Shape Crystals Birefringence Disease associations MSU 2 \200\22310 Needle, rod Strongly negative Acute and chronic gout CPPDD 2 \200\22310 Rhomboids, rods Weakly positive CPPDD crystal deposition disease, OA Apatite-like clumps 5 \200\22320 Round, irregular None Periarthritis, OA, clumps Calcium oxalate 2 \200\22310 Polymorphic, Positive Renal failure dipyramidal Cholesterol 10 \200\22380 Rectangles, needles Negative or positive Chronic RA or OA Depot glucocorticoids 4 \200\22315 Irregular rods, rhomboids Strongly positive or negative Iatrogenic post-injection \202 are Lipid liquid crystals 2 \200\2238 Maltese crosses Strongly positive Acute in \202 ammation, bursitis MSU = monosodium urate; CPPDD = calcium pyrophosphate dehydrate. CHAPTER 2 Investigation of rheumatic disease 43 \200 Identi \201 cation of crystal arthropathy. Identi \201 cation of septic arthritis. Micro-organisms can be identi \201 ed in 85% of clinically infected aspirates. Gram staini ng should be performed on aspirates to exclude infection by Gram-positive organisms, which account the majority of joint infections. Gram nega- tive organisms and organisms in previo usly or partially treated effusion may be dif \201 cult to detect. Further reading Dieppe P, Swan A. the identi \201 cation of synovial crystals in synovial \202 uid. Ann Rheum Dis 1999; 58: 261 \200\2233. Use of synovial \202 uid examination Examination of synovial \202 uid is most useful. \200 To distinguish non-inflammatory joint disease from in \202 ammatory causes. CLINICAL NEUROPHYSIOLOGY 44 Clinical neurophysiology De \201 nition Clinical neurophysiology is the diagnostic study of evoked and spontaneous bioelectrical signals from the central and peripheral nervous systems and from skeletal mus cle. It encompasses nerve conduction studies (NCS), needle electromyography (EMG), electroe ncephalography (EEG) and evoked central, and cortical responses (SSEPs, VEPs and BAEP). In the context of rheumatology only those aspects related to the study of the peripheral nervo us sys- tem and neuromuscular function are most often required. motor response distally. Any delay in the time taken for this re \202 ex (F latency) with normal distal conduction implies proximal slowing and demyelination. H re \202 ex The Hoffman re \202 ex (H re \202 ex) is used in a similar way, but is a ph ysiological response dependent on the stretch re \202 ex arc. It is the neurophysiological counterpart of the tendon re \202 ex. Other techniques Repetitive motor nerve stimulation is used to study the function of the ne uromuscular junction. Stimulation at a rate of 3 Hz normally elicits a compound muscle acti on potential of near identical amplitude with each successive stimulus. If there is failure of transmission at the neuromus- cular junction, as occurs in myasthenia gravis, the ampli tude of the compound action potential progressively falls with each stimulus, producing an amplitude \200\230decrement \200\231. Nerve conduction study Action potentials and conduction velocity Action potentials are evok ed by stimulating a peripheral nerve with a supra-maximal electrical square wave current of 0 \200\223100 mA usually of 0.1 ms duration (in some circum- stances the duration may be i ncreased up to 1 ms). The resultant evoked action potential is recorded with surface electr odes at a measured distance from the stimulating surface electrode. The amplitude of the ev oked response is recorded and the conduction velocity calculated. The action potential reco rded is a compound action potential generated by the summation of all the individual axon a ction potentials in a particular nerve or muscle. Needle electromyography With a needle electrode placed in a muscle the individual muscle \201 bre or motor unit action potentials can be recorded in response to a voluntary contrac tion (a motor unit is the group of muscle \201 bres supplied by one axon). The shape, dur ation, \201 ring rate, and amplitude of the individual action potentials are assessed. At maximal voluntary contraction the number of motor units is assessed by measuring the ampli tude of the overall envelope of electrical activity referred to as the interference pattern . Although there are objective quantitative techniques for this, in routine clinical practi ce this assessment is most often performed subjec- tively by observation of the action pote ntial representation on a display and through a loudspeaker. EMG is used to determine if a de \201 cit of motor function is secondary to nerve dysfunction (neurogenic) or due to pri mary muscle disease (myopathic). It also allows one to work out the anatomy of a nerve lesi on. Both sensory nerves and motor nerves can be studied. The amplitude of the compound action p otential gives an estimate of the number of axons stimulated. Each nerve and muscle has its own normal reference range for ampli- tude. Sensory amplitudes are measured in microvolts ( V) and motor amplitudes in millivolts (mV). The sensory ref- erence ranges are very wide and dependent on body weight, occupation, age and race. Conduction velocities are measured to the onset of the action potential and are those of the fastest axons stimulated, giving information about the integrity of the myelin. Conduction velocities are much less variabl e between patients and nerves. In the upper limb velocities are in the range of 50 \200\223 60 m/s, whereas in the lower limb the velocities are generally slower, around 40 \200\22350 m/s. Only the largest myelinated \201 bres can be studied by routine nerve conduction. Spontaneous activity is initially recorded. The muscle being studied must be completely rel axed. Normally, a muscle should be near silent on insertion of the needle. If one is near t he neuromuscular junction, a characteristic \200\230end plate noise \200\231 is heard. In acutely denervated muscle, myositis and many myopathies, muscle \201 bres generate sponta neous low amplitude very brief potentials called \201 brillations, which are a relatively non-speci \201 c feature of disturbed muscle physiology. Fibrillations may occur from mon ths to years if a denervated muscle does not reinnervate. Sensory action potentials (SAP) are measured with surface electrodes over the sensory nerve at a measured distance from the stimulating electrode allowing calcula- tion of the conduc tion velocity (CV). Motor function is studied by stimulating a nerve and measuring the elic ited compound muscle action potential (CMAP) amplitude recorded with surface electrodes ove r a muscle. The time taken between stimulus and response is the distal motor latency (DML). Motor conduction velocity (MCV) is deter- mined between any two accessible points along a nerve, which can be divided into multiple segments along the limb from the most distal stim ulus point up to the nerve root. This allows the demonstration of any focal slowing, motor conduction block or patchiness of abnormality. Other spontaneous activity is also seen which may imply more speci \201 c diagnoses. Spont aneously \201 ring motor units (fasciculations) when seen infrequently are normal, but if plentiful they suggest chronic, but ongoing denervation as seen in motor neuron disease. S ome types of spontane- ous and rapidly \201 ring motor units, complex repetitive discharg es, and myokimic or neuromyotonic discharges may be seen in proximal compressive lesions, d enervation and peripheral demyelination. Myotonic discharges are seen with clinical myotoni a. F wave Although in principle very proximal conduction velocities can be measured, the laten cy of the F wave is most often used as an indirect measure of proximal conduction. The F wa ve is a non physiological re \202 ex dependent on the retrograde stimulation of the motor nerve. A motor action potential can travel the wrong way along the axon to the anterior hor n cell where it can generate a re \202 ex action potential which then travels back down th e motor axon in the normal physiological direction evoking a recordable Acute denervation Acute denervation from any cause results in the reduction of the number o f motor units that can be activated and thereby also a reduction of the interference patter n. Any remaining motor units will \201 re more rapidly than normal to compensate. The mor phology of these units will CHAPTER 2 Investigation of rheumatic disease 45 nevertheless remain normal for several weeks until the muscle becomes chronically denervate d. Chronic denerva- tion results in the reinnervation of previously denervated motor units by axonal regeneration and intra-muscle collateral axonal sprouting, with consequent increa se in their amplitude and complexity resulting in polyphasia. Radiculopathy Study of patients with possible radiculopathies is often requested. This is u sually to exclude an alternative diagno- sis as MRI scanning is a more appropriate investig ation to show a root lesion. Nevertheless, neurophysiology may con \201 rm a radiculopathy by demonstrating a normal der- matomal sensory response accompanied by denervation changes con \201 ned to muscles supplied by the correspond- ing myotome. Root lesions are usually proximal to the dorsal root ganglion (preganglionic) resulting in a normal functioning dis tal sensory axon despite sensory distur- bance or numbness. Any lesion distal to the dorsal root ganglion is referred to as post-ganglionic. Muscle disease Primary muscle disease is characterized by the presence of many low amplitud e and highly polyphasic motor units that \201 re very easily and rapidly in response to v oluntary activa- tion, but with the generation of low levels of force as assessed by the ne urophysiologist. This results in a very full interference pattern of low amplitude. Myopathy Needle EMG is frequently requested for the assessment of possible myopathic condit ions, such as polymyositis and Statin, induce muscle disease. It is a very sensitive method and should be performed prior to muscle biopsy as it may direct which muscle to sample. My opathic needle EMG abnormalities are, however, seldom found in the absence of weakness. Mil d or even modest rises in creatinine kinase may not be accompanied by clear EMG changes if there are no other clinical abnormalities. Speci \201 c conditions Carpal tunnel syndrome and other entrapments The neurophysiologica l examination of patients with carpal tunnel syndrome (CTS) represents a paradigm of neuro- physiology and of other entrapment neuropathies. The aim is to con \201 rm the focal natu re of the neuropathy at the wrist and grade its severity. The median nerve SAP is nor- mall y recorded by stimulating digit 2 or 3, and recording over the median nerve proximal to the carpal tunnel. In a mild or early neuropathy only slowing of conduction may be seen due to a degree of demyelination, but as the condi- tion progresses axonal degeneration occurs wi th a fall in SAP amplitude. The median nerve SAP is compared with either the ulnar or radia l SAP. The DML to abductor policis brevis is measured to determine the degree of distal mot or slowing. As with sensory conduction evidence of motor slowing and demyelination normally occurs before loss of axons and CMAP amplitude reduction. A variety of short segment nerve studies are used to demonstrate focal carpal tunnel slowing such as a median palm to wrist sensory conduction velocity and a comparison of the DML from the second lumbrical (median innervated) to that of the second interosseous (ulnar innervated) muscles. End stage carpal tunnel syndrome results in the loss of any recordable motor or sensory response distally p reventing con \201 rma- tion of the focal nature of the original lesion. Neurophysi- ology for carpal tunnel syndrome is not usually required for diagnosis but is needed for plannin g treatment and predicting outcome. What to tell patients Clinical neurophysiology examination involves the use of small electr ical currents to stimulate nerves in order to assess the cause of symptoms. The electrical currents used are safe and feel a bit like a TENS machine or a muscle toner. Special care i s needed with pacemakers and patients may need cardiac monitoring during the examination an d a pacemaker check afterwards. The presence of implantable de \201 brillators is a signi \201 cant contraindication. Pregnancy is not a contraindication to electrical stimulation. Needle EMG is often likened to acupuncture and is of similar discomfort to a venepuncture. Warfarin is a relative con- traindication to needle examination and a recent INR (less tha n 2.5) is desirable. Some patients \201 nd the examination uncomfortable and they should be warned about this, but it should not be over emphasized as anxiety prior to the examinat ion undoubtedly increases the discomfort. Acknowledgements My thanks to Dr Julian Blake for his help in preparing this chapter. With some entrapment nerve lesions conduction block may be seen. With an acute lesion of th e ulnar nerve at the elbow or common peroneal nerve at the \201 bular head, it may be pos sible to demonstrate a normal functioning nerve segment distal to the lesion by virtue of n ormal SAP and CMAP amplitudes and CV, but with slowing of CV through the compressed region. With stimulation proximal to the lesion there is attenuation of motor and sensory amplitud es indicating a segment of signi \201 cant demyelina- tion. If left untreated such lesions may progress to axonal degeneration and loss of focal slowing making it dif \201 cult to localize the site of entrapment as with late carpal tunnel syndrome. Further reading Neuromuscular Home Page, Neuromuscular Diseases Center, Washington Universi ty, St Louis, MO USA. Available at: http:// neuromuscular.wustl.edu British Society for Clinical Neurophysiology. Available at: http:// www.bscn.org.uk American Association of Neuromuscular and Electrodiagnostic Medicine. Available at: http://www.aanem.org Preston DC, Shapiro BE. Electromyography and Neuromuscular Disorders, 2nd edn. Philadelphia : Elsevier, Butterworth Heinemann, 2005. Making the best use of Clinical radiology service. (Sixth Ed.). Royal College of Radiologists 2007. This page intentionally left blank 47 Chapter 3 Organ involvement in rheumatological disease The eye 48 The chest 54 The heart 66 The kidney 74 The gut and hepatobiliary disease 82 The nervous system 90 The skin 98 THE EYE 48 The eye Although serious eye problems are rare in rheumatology clinics, failure to spot warning sig ns and symptoms can have catastrophic consequences for the patient. This chapter will consi der rheumatological conditions affecting the eye and highlight those, which require urgent referral and treatment. High dose immunosuppressi on is often required to prevent ocular pathology due to the very limited ability of the eye to recover function following damage. Classi \201 cation Table 3.1 Anatomical classi \201 cation of eye involvement in rheumatological disease Uveitis Scleritis Ocular surface Optic Retinal changes Other neuropathy Rheumatoid arthritis No Painful or painless PUK, dry eye Very rare Very rare retinal vasculitis Anterior scleritis Conjunctivitis Ankylosing spondylitis Anterior uveitis, bilateral in 80% hypopyon is common Systemic lupus erythematosus Yes Dry eye Very rare CWS, hemorrhages, oedema, vascular occlusion Systemic sclerosis Dry eye Sj grens syndrome Dry eye Orbital myositis Dermato- and polymyositis Yes CWS, hemorrhages, oedema Cerebral sinus thrombosis (bilateral papilloedema) Beh et \200\231s disease Panuveitis, hypopyon is common Rarely Rare Retinal vein occlusions, white ischaemic retinal patches Relapsing polychondritis Yes 43% of RP PUK Rare Rare CWS, hemorrhages Polyarteritis nodosa Rarely Yes PUK Rarely AION CWS, exudates Rarely orbital in \202 ammation Facial nerve palsy Sarcoidosis Acute or chronic pan-uveitis Rarely Dry eye Yes Choroidal granulomas, periphlebitis, optic neuropathy Rarely Conjunctivitis (rarely keratitis) Reactive arthritis Mainly anterior uveitis (in 30%) often unilateral Giant cell arteritis Rarely Yes CWS occasionally Transient obscurations 10% Wegener \200\231s granulomatosis Rarely causes uveitis Yes PUK Yes Retinal vasculitis Orbital involvement common Juvenile idiopathic arthritis Chronic anterior uveitis Glaucoma, band keratopathy Anti-phospholipid syndrome (APS) Rarely AION Retinal vascular occlusions Amaurosis fugax, TIA Psoriatic arthritis Anterior uveitis Rarely In \202 ammatory bowel disease Anterior or posterior uveitis Rarely Abbreviations: PUK; Peripheral ulcerative keraitis; CWS = Cotton wool spots; AION = anterio r ischaemic optic neuropathy. CHAPTER 3 Organ involvement in rheumatological disease 49 De \201 nitions and disease associations Nomenclature describing anatomy of the eye is sho wn in Figure 3.1. Commonly due to diabetes or hypertension, but also seen in association with rheumatological conditions, such as Beh et \200\231s, SLE, antiphospholipid syndrome (APLS), Sarcoidosis, etc. Conjunctivitis Infection or in \202 ammation of the conjunctiva (usually viral, bacterial or allergic). Sarcoidosis Sarcoid can cause granulomas to form anywhere in the eye including the optic ne rve, lacrimal gland or eyelids. Granulomatous uveitis is typical. Sarcoid is arguably the c ommonest cause of posterior uveitis in rheumatology patients and is a cause of retinovascul ar disease. Blepharitis In \202 ammation of eyelid margins often with colonization of \200\230harmful bacteria \200\231, such as staphylococcus. Exacerbates dry eye problems. Episcleritis In \202 ammation of episclera. Is usually idiopathic, but can be seen in rheu matoid arthritis (RA), spondylarthropathies (SpAs), and gout. Episclera Sclera Ciliary body Choroid Scleritis In \202 ammation of sclera, may be anterior (red eye) or pos- terior (eye may be white), nodular, diffuse, necrotizing or non-necrotizing. Retina Lens Eyelid Optic nerve 30 \200\22350% cases are idiopathic but scleritis can be associated with RA, Wegner \200 \231s granulomatosis (ANCA-associated vasculitis, AAV), SpAs, relapsing polychondritis (RP) , poly- arteritis nodosa (PAN), systemic lupus erythematosus (SLE), Beh et \200\231s, sarc oidosis, and very rarely ulcerative colitis, gout, Mycobacterium tuberculosis (MTB), Lyme d isease and syphilis. Vitreous humor Iris Aqueous humor Peripheral ulcerative keratitis In \202 ammation, thinning, and ulceration of sclera and c ornea (corneal in \202 ammation = keratitis). Is similar to scleritis. Anterior uveitis (i ritis, iridocyclitis) In \202 ammation centered on the anterior chamber of the eye/ iris ( may be granulomatous or non granulomatous). Inter- mediate uveitis is in \202 ammation cen tered on the vitreous. Occurs in SpAs, sarcoidosis, Lyme disease, MTB, multiple sclerosis, pars planitis and in association with juvenile idiopathic arthritis (JIA). Many cases are i diopathic however. Conjunctiva Skin Cornea Posterior uveitis In \202 ammation centered on the posterior chamber of the eye/retina/cho roid. Panuveitis \200\223 posterior uveitis with vitreous cells and anterior uveitis. Post erior uveitis occurs in sar- coid, Beh et \200\231s (esp. Turkish). It occurs, too, in SLE , PAN, and dermatomyositis, but is very rare. Figure 3.1 Diagrammatic representation of the eye shown in cross-section. SLE May cause cotton wool spots in retina. Vascular occlusion, such as blockage of the cent ral retinal artery may occur presenting with sudden onset severe loss of vision in one eye. Retinal neovascularization with subsequent vitreous hemorrhage may also occur. Cataract Opaci \201 cation of the lens. Common in elderly patients, secondary to glucocort icoids (GCs) or uveitis. Rheumatology drug associated effects on the eye \200 Glaucoma Raised intraocular pressure with associated visual \201 eld loss and optic disc cupping. Glaucoma is often secondary to GC use and uveitis, particularly in JIA and sarcoid osis. It is more common if there is a family history of glaucoma or in short-sighted patien ts. GCs cause cataract, glaucoma, and rarely central serous retinopathy. Hydroxychloroquine rar ely causes a bullseye appear- ance maculopathy with retinal cell death. Bisphosphonates (es pecially pamidronate) have been reported to cause uveitis or unilateral scleritis. Etanerce pt may rarely be associated with uveitis. Potent immunosuppression (e.g. cyclophosphamide) increases risk of viral retinitis (HSV, CMV), which may present with blurred vision, \201 eld loss, \202 ashing lights, or \202 oaters. Although rare, this is potentially very serious and merits immediate referral for ophthalmological examination. Penicillamine can c ause myasthenic diplopia. Retinovascular disease Causes. In \202 ammation and/or occlusion of retinal blood vessels, branch, or central retinal artery occlusion or vein occlusion. \200 \200 Retinal vessel in \202 ammation is usually referred to as retinal vasculitis, whilst reti nitis refers to mainly viral retinal infections (cytomegalovirus, CMV) or as a misnomer in retinitis pigmentosa. Maculopathy is a non-speci \201 c term denoting any pathol- ogy aff ecting the central retina (e.g. diabetes, genetic conditions, ageing change). THE EYE 50 Risk factors \200 superficial episcleral vessels are constricted by the phenylephrine. The scleral vessels ar e too deep to be affected (phenylephrine causes blurred vision and pupil dilation for 8 h). With a direct ophthalmoscope, detect the presence or absence of optic disc swelling, atrop hy, disc cupping (in glaucoma), retinal hemorrhages, and cotton wool spots. Large keratic p recipitates (KPs) will be visible with an oph- thalmoscope. Pull lower lid down to look for a hypopyon. Pus in the anterior chamber (hypopyon) is typically seen in HLA B27 positive a nterior uveitis, particularly with AS. Also seen with Beh et \200\231s and endophthalmitis . To detect mild anterior or posterior uveitis requires examination with a slit lamp, as ce lls in the anterior chamber are not visible with a direct ophthalmoscope. Confrontation vis ual \201 eld testing will only pick up gross pathology like a homonymous hemianopia from a CVA. It will not detect early glaucoma. A relative afferent papillary defect denotes seri ous pathology affecting the visual pathway between the optic chiasm and the retina (GCA, sa rcoid optic neuropathy, retinal detachment). A cloudy cornea can occur with very high intra ocular pressure (acute glaucoma), confluent KPs (uveitis), infection, trauma, band keratopa thy, and corneal decom- pensation (post-surgery). Irregular pupil shape from posterior syne chiae or KPs imply that the patient has had anterior uveitis. They do not always disappear following treatment sometimes becoming pigmented and permanent. Only treat if active uveiti s is con \201 rmed with slit lamp examination. Human lymphocyte antigen (HLA) B27 is strongly associated with anterior uveitis. All JIA pa tients should be screened for uveitis. In giant cell arteritis (GCA), in 70% of untreated c ases, visual loss in one eye is followed within 1 week by visual loss in the second eye. In RA, rheumatoid factor (RF) seropositivity is a risk factor for scleritis. \200 Clinical features Key features in the history \200 Presence/severity of pain: \200 \200 photophobia is common in uveitis; if woken from sleep by severe pain \200\230like someone drilling into my eye socket \200\231 then consider symptom very typical for scleritis; mild tenderness to touch can mean episcleritis, though scleritis is more severe and serious; gr ittiness and stinging suggest dry eye or other ocular surface problems; blepharitis is the commonest cause of dry eye symptoms with grittiness, watering, crust- ing of eyelid margins , mild redness with normal vision. [Warning: blepharitis is so common that many patients wi th serious eye problems also have blepharitis \200\223 it is a diagnosis of exclusion.] Visual disturbance: with loss of vision for a few seconds only consider GCA. Blurred vision can be due to uveitis, cataract, retinovas- cular disease, and rarely scleritis. Never dia gnose episcleritis, blepharitis, or conjunctivitis if vision is blurred and does not clear on blinking. A sticky discharge occurs with conjunctivitis, is copious, foul smelling, and purulent in gonorrhoeal conjunctivitis, and manifests as stringy threads in allergic conjun ctivitis. History of use of eye drops/other ophthalmic prepara- tions might suggest allergi c conjunctivitis. It causes red itchy eye and skin around lids (develops if patients are al lergic the preservative in arti \201 cial tear drops). A pre- servative-free preparation s uch as celluvisc 0.5% should be tried. New headache, scalp tenderness, jaw claudication, to ngue claudication, shoulder/hip girdle stiffness may indicate GCA [with or without polymyal gia rheumatica (PMR)). More often, patients have had sudden loss of vision in one eye to c ount \201 ngers vision or worsens with a recent onset new headache. Fundoscopy Macula Cystoid macular oedema (CMO; \202 uid cysts at fovea with a petalloid a ppearance) occurs with uveitis but is dif \201 cult to see with an ophthalmoscope and is b est demonstrated using ocular coherence tomography or \202 uorescein angiog- raphy. Flame hemorrhages and cotton wool spots require investigation to check blood pressure (BP) and f or hyper- glycaemia before looking for a vasculitic or autoimmune process. Disc GCA may present with severe unilateral loss of vision, an afferent pupillary defect an d a pale swollen optic disc caused by arteritic anterior ischaemic optic neuropathy (occlus ion of the small blood vessels supplying the optic nerve anteriorly in the orbit). Retinovascular disease \200 Key features on examination All patients complaining of any eye symptoms at all must have s ome record of their visual acuity in each eye (Snellen chart ideally pinhole or if not a vailable ability to read small print with glasses on). \200 Asymptomatic vascular sheathing is most commonly caused by sarcoidosis (venous candle wax dripping ). Arterial sheathing is rare, but may be seen with SLE, PAN, AAV, Beh et \200 \231s, syphilis, and acute retinal necrosis. Vascular occlusions are usually painless and m ay not be noticed by the patient (branch retinal vein occlusions affecting peripheral veins ) or may cause profound visual loss as in central retinal artery occlusion. Vein occlusions with uveitis suggest Beh et \200\231s, sarcoidosis or syphilis. Vein occlusions without u veitis are usually secondary to atherosclerosis in the retinal artery, which compresses the vein as it crosses it on the retina. Retinal arterial occlusion is commonly secondary to e mboli from the carotid arteries, but can occur in GCA, SLE and some forms of vasculitis. Red eye is caused by conjunctivitis, blepharitis, episcleritis, anterior scleritis, or uvei tis (not always). White eye is from posterior scleritis and some chronic uveitides (e.g. sa rcoid, JIA, intermediate uveitis). Check for distribution of redness . Diffuse is unhelpfu l in differentiating cause. Quadrantic is typical for episcleritis, scleritis or trichiasis , whilst circumlimbal \202 ush occurs in anterior uveitis, but is not a reliable sign. Th e redness of scleritis will persist after one drop of 10% phenylephrine is administered, wh ereas the redness of episcleritis will disappear after 10 min as the more CHAPTER 3 Organ involvement in rheumatological disease 51 If taking a swab for conjunctivitis then culture for Chlamydia, as well as the usual organi sms. Central retinal artery occlusion results in \200\230count \201 ngers \200\231 vision or worse, and a pale retina with a cherry red spot at the fovea. The retinal appearance return s to normal within 2 weeks. Vein occlusions do not allow blood to leave the eye, hence ther e are multiple retinal hemorrhages, often \202 ame-shaped. Histology \200 \200 Orbital biopsy may be required to diagnose AAV. Sarcoid granulomas can be seen on conjuncti val biopsy or lacrimal gland biopsy in dry eye patients. Temporal artery biopsy may be usef ul in GCA, although a negative biopsy does not exclude the diagnosis. Conjugate gaze/double vision Unless long-standing double vision requires that the patient i s referred to an ophthalmologist. \200 Other laboratory tests Tests requested should be determined once the ophthal- mological dif ferential diagnosis has been formed. All systemic rheumatological diseases associated with eye lesions are appropriately evaluated with full blood count (FBC), ESR, CRP, LFTs, U&Es, and creatinine. \200 Usually caused by thyroid eye disease, cranial nerve palsies, decompensating squint, decomp ensating congenital fourth nerve palsy, or trauma. Rare causes of diplopia that could prese nt in the rheu- matology clinic include rheumatoid nodule on superior oblique tendon causin g vertical diplopia, penicillamine- induced myasthenia, orbital mass from AAV, central nerv ous system (CNS) lesions, or a nerve palsy from vasculitis, Whipple \200\231s, sarcoidosis, Lyme disease, Beh et \200\231s, or MTB. ESR, FBC, LFTs, and CRP should be tested if GCA sus- pected. A normal ESR and/or CRP does n ot rule out the diagnosis. A raised platelet count is suggestive in younger patients. A rai sed ACE is associated with, but not speci \201 c for sarcoid. Some people with sarcoid hav e an ACE in the reference range. If AICTD suspected then consider checking ANA, ENAs, C3, a nd C4, RF, a functional assay for lupus anticoagulant (e.g. Dilute Russell Viper Venom Test , DRVVT) and aCL antibodies. If RA suspected check RF and CCP antibodies. General examination The approach to a general examination will depend on the history and oc ular \201 ndings, but should include looking for joint pathology (e.g. RA), skin (Psorias is, erythema nodosum, vasculitis, scalp tenderness), lungs (sarcoidosis, AAV). All patients with scleritis should have BP and urinalysis to exclude renal involvement, which may be li fe threatening. Treatment Uveitis \200 Investigations Slit lamp examination Dry eye can be detected using 2% \202 uorescein drop s. These reveal inferior punctuate staining and sometimes corneal droplet like threads call ed \201 lamentary keratitis. Rose \200\223Bengal drops cause eye pain and are best avoide d. Anterior uveitis can usually be managed by topical gluco- corticoid (GC) eye drops and dila ting drops (cyclopen- tolate) to prevent posterior synechiae forming). A reducing course of GCs over 5 \200\2236 weeks is typical, although some patients require GC eye drops for man y years to prevent \202 are-ups. Occasionally subconjunctival GC injections are required. Children with JIA can get anterior uveitis which causes damage to the eye without the pati ent having symptoms or causing red eye (see below). Posterior uveitis may also require orbi tal \202 oor depot steroid injections (triamcinolone), systemic steroids, steroid sparing agents (ciclosporin, mycophenolate mofetil, tacrolimus, and azathioprine) and biologics (i nf- liximab preferred to etanercept in eye patients). Intravitreal GC injections are also u sed. A rare complication of posterior uveitis is the develop- ment of a choroidal neovasacu lar membrane \200\223 this presents with unilateral blurred vision and distortion (assesse d with Amsler grid). Urgent ophthalmology opinion is needed to consider increased immunosup pression, photodynamic therapy or the use of intra-vitreal anti-VEGF agents. Sarcoid usuall y responds well to topical and systemic steroids, methotrexate may have some advantages as a steroid sparing agent in this condition. Sarcoid uveitis often is chronic. HLA B27 associ ated anterior uveitis has a relapsing remitting course. Beh et \200\231s patients often re quire high dose systemic GCs and ciclosporin. Azathioprine reduces the incidence of ocular attacks. Chlorambucil may cause long-term remis- sion, but causes infertility. In \202 ixi mab or interferon-A2a may prove useful for ocular disease in the future. About 90% of patie nts with ocular Beh et \200\231s go blind in 4 years if not treated. Schirmer \200\231s test (Figure 8.4) A Schirmer strip ( \201 lter paper) is tucked under t he lower eyelid and soaks up the tears. The length of staining in mm gives a measure of tea r production. Less than 5 mm wetting in 5 min denotes aqueous tear de \201 ciency (as seen in Sj gren \200\231s), 5 \200\22310 mm is equivocal, greater than 10 mm is normal (withou t anesthetic eye drop use). Tonometry All uveitis patients need their intraocular pressures checked by Goldman tonometr y. Digital tonometry (using 2 \201 ngers to press on the eyeball) is only reliable to dis tin- guish between normal pressure (<21 mmHg) and extremely high pressures (>45 mmHg). Fluo rescein angiography Is used to investigate uveitis (CMO and vasculitis) and visual loss in scleritis. May also show delayed choroidal perfusion in cases of visual loss in suspected G CA. Ocular coherence tomography (OCT) Allows 3D imaging of the retina down to the level of the choroid. Very useful for showing retinal \202 uid (CMO). Microbiology \200 Borrelia serology is rarely positive, but worth doing in endemic Lyme Disease areas. TPHA i s always worth checking as it alters treatment. If viral retinitis is suspected, then a vit reous tap should be taken and sent for PCR for varicella-zoster, CMV, Epstein Barr virus (E BV), syphilis, and toxoplasmosis. \200 THE EYE 52 dilute baby shampoo. Ocular chloramphenicol bd for 2 weeks GC eye drops when necessary. Oral doxy- cline can be used in more severe cases with rosacea. Scleritis and episcleritis \200 Episcleritis is usually self-limiting or resolves with \202 urometholone eye drops (mild GC) or oral non-steroi- dal anti-in \202 ammatory drugs (NSAIDs). It is sensible to refer to an ophthalmologist to check diagnosis unless there is a convincing and documented histor y of previ- ous episcleritis. Scleritis may resolve with an NSAID or systemic GCs (reducing course over many months). Severe cases of scleritis may need IV methylprednisolone 1 g dai ly for 3 days followed by oral GCs and GC-sparing agents. Cyclophosphamide may be needed in very aggressive cases. Urgent ophthalmology referral is required as severe scleritis cases can rapidly result in scleral melting, globe perforation, and loss of vision. PUK is treat ed along similar lines to scleritis. There is no ocular treatment for scleromalacia perfora ns (painless necrotizing scleritis in late stage RA). RA scleritis patients have an increas ed risk of mortality. Surgery \200 Cataract surgery in patients with uveitis requires ade- quate GC cover and management by an ophthalmologist with some experience of managing uveitis. Lacrimal duct plugging/ablation is useful in more severe cases of dry eye. Intraocular GC slow-release devices are being de veloped but have a high rate of secondary glaucoma. Retinovascular disease in AICTDs/vasculitis Active retinopathy in the context of an AICTD o r vasculitis should prompt a review of disease activity by both medical ophthalmologist and rheumatologist. The retina is the only part of the body, apart from the nailfolds, where c apillaries vessels can be viewed directly. \200 Care should be taken to distinguish hypertensive retinopathy from that caused by systemic v asculitis. SLE retinopathy usually has a good prognosis for vision, although a small group has an occlusive vasculopathy and cerebral vasculitis with a poor prognosis. Giant cell arteritis In suspected cases with ocular symptoms immediate ophthalmology referr al is mandatory. Also do not delay starting glucocorticoids (GCs), while waiting for an oph - thalmologist to review the patient or a biopsy. In GCA it is very unusual for any signi \201 cant visual recovery to take place once vision is lost. \200 Juvenile idiopathic arthritis \200 \200 Anterior uveitis can be asymptomatic. JIA-associated uveitis can start soon after the onset of the arthritis or may already be present at the time of diagnosis of JIA. It can be seve re with few symptoms. Referral for ophthalmological screening by a specialist experienced i n seeing children with the condition is therefore urgent. Children should be screened by an ophthalmologist according to the BSPAR protocol (see Assessment tools, below). Treatment i s challenging and children can go blind with this condition. Systemic GCs, eye drops, and m ethotrexate have been used extensively. If methotrexate is discontinued for any reason then the ophthalmologist should be informed as more frequent ocular screening is required at th is point In addition to chronic anterior uveitis, ocular damage and even blindness can be c aused by cataract, secondary glaucoma, band keratopathy and ultimately phthisis bulbi. Observational studies support the use of high dose GCs in GCA. Recently, guidelines on the management of large vessel vasculitis have been produced by EULAR (Mukter et al., 2008). In patients without ocular symptoms, oral GCs starting at 0.7 \200\2231 mg/kg (maximum dose 6 0 \200\22380 mg) should be prescribed. In patients with ocular symptoms IV methyl- predniso lone 1 g daily for 3 days should be used in addition to oral GCs. The headache should resol ve rapidly (<48 h). A recent randomized study suggested that use of IV methylprednisolone ( 15 mg/kg) for 3 days in addition to oral prednisolone 40 mg/day permitted more rapid GC tap er. Oral GCs should be tapered quickly aiming for 10 mg/day at 6 months. In patients with \202 uctuating visual loss, plasma expanders, fragmin, aspirin, lying the patient down wit h foot of bed raised, and oral acetazolamide to reduce intraocular pressure, have been trie d. Data from robust studies is lacking however. \200 Resources Assessment tools A reading chart (test with reading glasses on and record distanc e, e.g. 20 cm) or Snellen chart should be available to check visual acuities. Keratoconjunctivitis sicca Most patients bene \201 t from eye drops. There are many differ ent preparations from which to choose. \200 Hydroxychloroquine screening \200 Short-acting preparations contain polyvinyl alcohol (SnoTears, Liqui \201 lm) or carboxyce llulose (hypromellose, Tears Naturale). Longer-acting preparations contain carbomer gels (e .g. Viscotears, Geltears) or paraf \201 n (e.g. Lacrilube, Lubri-Tears); these are stickie r and patients may prefer to use them at night. Some patients are intolerant of preservativ es in aqueous drops and preservative-free Liqui \201 lm may be tolerated. Blepharitis is c ommon and frequently exacerbates the symptoms of dry eyes. Treat with daily lid hygiene cle aning eyelid margins with a cotton bud dipped in