Joint aspiration and injection and synovial fluid analysis...Joint aspiration and injection and...

Best Practice & Research Clinical Rheumatology 27 (2013) 137–169

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Joint aspiration and injection and synovial fluidanalysis

Philip Courtney a,*, Michael Doherty b,1

aDepartment of Rheumatology, Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, UKbAcademic Rheumatology, Clinical Sciences Building, Nottingham City Hospital, Hucknall Road,Nottingham NG5 1PB, USA

Keywords:Intra-articular corticosteroidSynovial fluid analysisMonosodium urate crystalsCalcium pyrophosphate dihydrate crystals

* Corresponding author. Tel.: þ44 0115 9627697E-mail addresses: [email protected] (P.

1 Tel.: þ44 0115 8231756; fax: þ44 0115 823175

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a b s t r a c t

Joint aspiration/injection and synovial fluid (SF) analysis are bothinvaluable procedures for the diagnosis and treatment of jointdisease. This chapter addresses (1) the indications, technicalprinciples, expected benefits and risks of aspiration and injectionof intra-articular corticosteroid and (2) practical aspects relating toSF analysis, especially in relation to crystal identification. Intra-articular injection of long-acting insoluble corticosteroids is awell-established procedure that produces rapid pain relief andresolution of inflammation in most injected joints. The knee is themost common site to require aspiration although any non-axialjoint is accessible for obtaining SF. The technique involves onlyknowledge of basic anatomy and should not be unduly painful forthe patient. Provided sterile equipment and a sensible, asepticapproach are used, it is very safe. Analysis of aspirated SF is helpfulin the differential diagnosis of arthritis and is the definitivemethod for diagnosis of septic arthritis and crystal arthritis. Thegross appearance of SF can provide useful diagnostic informationin terms of the degree of joint inflammation and presence ofhaemarthrosis. Microbiological studies of SF are the key to theconfirmation of infectious conditions. Increasing joint inflamma-tion associates with increased SF volume, reduced viscosity,increasing turbidity and cell count and increasing ratio of poly-morphonuclear:mononuclear cells, but such changes are non-specific and must be interpreted in the clinical setting. However,

; fax: þ44 0115 9627709.Courtney), [email protected] (M. Doherty).7.

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P. Courtney, M. Doherty / Best Practice & Research Clinical Rheumatology 27 (2013) 137–169138

Table 1Indications for joint aspiration.

Diagnostic(a) acute synovitis

� sepsis� crystals:

common: monosodium uratecalcium pyrophosphaterare: oxalate, cholesterol

(b) chronic arthropathy

� crystals (monosodium urate, calcium pyro

Treatment(a) common

� to reduce intra-articular pressure� injection of corticosteroid

(b) less common

� recurrent aspiration for sepsis

saline lavage for resistant arthropathy

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detection of SF monosodium urate and calcium pyrophosphatedihydrate crystals, even from un-inflamed joints during inter-critical periods, allows a precise diagnosis of gout and calciumpyrophosphate crystal-related arthritis.

� 2013 Published by Elsevier Ltd.

What are the indications for joint aspiration/injection?

Principal indications for joint aspiration and injection are listed in Table 1. It is particularly requiredfor the diagnosis andmanagement of the acute ‘hot red joint’, which is a medical emergency because ofthe morbidity and mortality related to septic arthritis. This largely relates to presentation with acutemonoarthritis but is also relevant to the patient with pre-existing chronic polyarthritis such as rheu-matoid arthritis who develops a ‘flare’ limited to one joint. It is only by aspirating synovial fluid (SF)that joint sepsis or crystal-associated synovitis (gout or pseudogout) can be accurately diagnosed.

Important clinical features that always require consideration of sepsis include:

� acute synovitis, especially in patients at increased risk of joint sepsis (rheumatoid arthritis (RA),diabetes and immunocompromised patients); sepsis most commonly, though not exclusively,occurs in joints with pre-existing damage;

� rapidly progressive symptoms in a single joint;� additive joint involvement (e.g., first metatarsophalangeal joint (MTPJ), followed by ankle and thenknee involvement on the same side);

� erythema overlying the joint (a sign of periarticular inflammation that particularly accompaniessepsis or crystals); and

� inflammatory pain in joints that are commonly asymptomatic if affected by other, non-septic,arthropathy (e.g., sternoclavicular joint).

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P. Courtney, M. Doherty / Best Practice & Research Clinical Rheumatology 27 (2013) 137–169 139

Frequent aspiration may be required as part of the management of septic arthritis. However, needleor arthroscopic lavage or surgical drainage should be undertaken if rapid reaccumulation or loculationresistant to simple aspiration occurs. A prosthetic joint should not be aspirated without priorconsultation with an orthopaedic surgeon or rheumatologist. Crystal arthritis can be diagnosed byaspiration of currently inflamed joints and also from asymptomatic joints during intercritical periods,and even from knees and first MTPJs that have not suffered acute attacks [1].

Aspiration of SF from a tense swollen joint, due to synovitis or haemarthrosis, may quickly relievesevere pain by reducing intra-articular pressure. In the situation of inflammatory synovitis, reac-cumulation of SF can be prevented (at least temporarily) by the intra-articular injection of long-actingcorticosteroids. If sepsis is a possibility, steroid injection should only be done after exclusion of sepsisby joint-fluid culture. However, SF cultures are almost never positive in the absence of clinical sus-picion of infection; hence, routine culture of aspirated SF is unnecessary [2]. A corticosteroid injectionmay avoid the requirement for additional systemic treatment or provide quick relief while slowdisease-modifying drugs take effect. In the circumstance of inflammatorymonoarthritis, intra-articulartreatment is most appropriate. Intra-articular corticosteroid (IAC) injection can also provide rapid painrelief in clinically un-inflamed joints with osteoarthritis (OA).

What are the general technical principles?

Setting

An aseptic technique is mandatory with sterile equipment. Gloves should be worn to protect theoperator, especially in high-risk situations such as human immunodeficiency virus (HIV) or hepatitis,but they need not be sterile if a no-touch technique is used. There is no need to gown up or go to theatreand it is perfectly acceptable to carry out the procedure in a general ward or outpatient clinic. However,considerable variation in practice occurs and audits have shown that between one-quarter and one-third of practitioners (rheumatologists, orthopaedic surgeons and primary-care physicians) routinelyuse sterile gloves [3,4] and some routinely use additional sterile precautions. Cawley and Morrisdemonstrated that simple swabbing with alcohol is as effective in killing skin flora as is chlorhexidinepreparation [5]. The risk of infection is very small with simple swabbing, sterile equipment and a no-touch technique. A retrospective survey in France suggested an overall risk of sepsis of 13 per millioninjections with the incidence being much lower if pre-packaged steroid syringes were used [6]. In aretrospective 10-year survey of septic arthritis in Nottingham (population 600,000) only three cases ofseptic arthritis possibly related to corticosteroid injection were identified [7].

Preparation of the patient

The patient should be positioned on a couch with the injection area supported sufficiently so thatthe muscles can comfortably relax. The surface anatomy and joint landmarks should be identified. Theoverlying skin should be cleaned with an alcohol swab. A no-touch technique is essential aftercleaning; hence, any mark to identify the point of entry should be made earlier. The point of entry canbemarked by a cross with the centre removed by the antiseptic swab. An alternativemethod is tomakea small indentation of the skin. Local anaesthetic, either as a anaesthetic gel/cream or as a coolingrefrigerant spray, is not usually applied to the skin for adults but is necessary for children.

Technical considerations

Large joints such as the knee and shoulder are aspirated using a 21-gauge (green) needle although alarger needlemay be required to readily aspirate very purulent fluid. A 23- or 25-gauge (blue or orange)needle is appropriate for smaller joints. Smaller syringes are easier to operate when aspirating jointsand it is often easier to disengage, empty and re-use a 20-ml syringe than to employ a larger barrel size.

If injection is also required the corticosteroid should be drawn up in a 2-ml syringe and kept close tohand capped with a sheathed needle. A ‘reciprocating’ syringe that has two barrels connected to asingle exit is reported to improve operator control of the needle, reduce likelihood of displacement and

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reduce procedure time [8]. Initial aspiration of SF was shown to improve the outcome in RA patientstreated with intra-articular steroid [9]. This study of 191 knee injections showed that the proportion ofrelapses over a 6-month follow-up period was significantly reduced if aspiration was performed priorto injection. However, if concomitant steroid injection is required it is best not to aspirate to completedryness as leaving a little fluid may reduce the risk of needle displacement. Furthermore, althoughaspiration to near dryness should be attempted for tense, acute effusions, the quadriceps may adapt itsproprioceptive acuity to chronic, large, knee effusions and complete emptying may cause destabili-sation of proprioception and ‘giving way’. Jones et al. have shown the uncertainty of correct injectionplacement in the absence of SF aspiration [10]. In this study a large proportion of injections were shownto be extra-articular by the concomitant injection of contrast medium. In another study Bliddal showedthat 9% of knee-joint injections were extra-articular [11]. A more recent study of subacromial injectionsshowed an accuracy of 70% [12] but, unlike the Jones et al. study [10], clinical improvement did notcorrelate with accuracy. At the end of aspiration the needle should be held firmly with one hand as thesyringe barrel is disengaged. The predrawn steroid syringe is then attached taking care not to displacethe needle. If there is resistance to injection the needle should be withdrawn slightly, the landmarksredefined and the needle then reinserted in the correct direction.

The commonly used preparations for intra-articular injection are the longer-acting hydrophobicsteroids such as methylprednisolone acetate (MPA) and triamcinolone hexacetonide. Hydrocortisoneacetate is shorter acting and less effective but has a role in some soft-tissue injections such as carpaltunnel syndrome [13]. Corticosteroid preparations such as MPA should not be mixed with localanaesthetic as this results in precipitation. At the end of aspiration or injection the puncture site shouldbe pressed with a cotton-wool ball until local skin bleeding has stopped.

Practice points

� Aseptic no-touch technique is mandatory.� There is no requirement to ‘gown up’ or go to theatre.� Gloves should be worn.� The patient should be positioned with the joint relaxed.� Avoid surface blood vessels or cellulitis at point of entry.� Aspirate tense, acute effusions to near dryness, but do not aspirate to complete dryness if aninjection is to be given or if it is a large, chronic, knee effusion.

� Steroid should not be injected against resistance.� Hydrophobic corticosteroids (triamcinolone acetonide and hexacetonide) are more effectivethan hydrocortisone.

� MPA should not be mixed with local anaesthetic.

What equipment is required?

The equipment required is listed in Table 2.

Table 2Equipment for Intra-articular corticosteroid injection.

Patient couchGlovesSterile swabsPrepacked sterile needles (19, 21 and 23 gauge) and syringes (2, 5, 10 and 20 ml)Single-dose sealed ampoules of injectable corticosteroidSingle-dose sealed ampoules of local anaesthetic (lignocaine 1% or 2%)Synovial fluid collection bottlesElastoplast or cotton-wool



What information should I give to the patient?

Explain the rationale and nature of the procedure to the patient. Include a clear discussion of theexpected level of discomfort and the symptom relief that may follow. The more relaxed and informedthe patient is, the better. Although aspiration involves a needle prick and some discomfort, in expe-rienced hands it should not bemuchmore uncomfortable than venepuncture. This is especially true forlarge joints such as the knee, ankle or glenohumeral joint and joints with significant effusions. Theprocedure is relatively quick and any discomfort should be short-lived.

If the joint is to be injected the risks and possible side effects should be discussed. The toxicity of steroidinjection is lowbut patients should bewarned regarding facialflushing (12%), post-injectionflare (15%) andsepsis (<1:78,000 risk). Although the risk of infection is very small indeed, individual cases continue to bereported, and the patient should be warned [6,7]. Subcutaneous atrophy is more of a concern with peri-articular injections but has been describedwith intra-articular injections, especially small-joint or complexinjections [14]. A small area of depigmentation may occur at the site of steroid injection. It is generallyproposed that the frequencyof injections shouldbenomore than3-monthlyalthough there isnoconclusiveevidence of any detrimental effect on cartilage or bone from steroid injection into an arthritic joint. A largecase series of long-term follow-up of childrenwith juvenile idiopathic arthritis, who had receivedmultipleinjections, failed to demonstrate anyadverse effect on the joint [15]. Raynauld et al. showed that therewereno deleterious effects from 3-monthly steroid injections for knee OA over 2 years [16].

There is some evidence of significant systemic corticosteroid absorption following intra-articular in-jection in an animal model [17], but this is unlikely to be clinically important in the majority of cases.Laaksonen et al. described alterations in plasma cortisol levels which persisted for at least 4 weeks,following IAC injection in children [18]. The authors suggested that this transient suppression ofendogenous cortisol may not be clinically important. Another concern is the possible contribution ofsystemic absorption of corticosteroid to osteoporosis but Emkey et al. reassuringly concluded that IAC hasno net effects on bone resorption inpatientswith RA [19]. Although systemic absorption raises some otherpotential concerns, such as temporary worsening of diabetic control [20], it can give symptomatic benefitto other joints. Improvement to the un-injected knee was demonstrated by McDonald et al. following IACof the knee using microwave thermography [21]. Therefore the patient may be informed that a smallamount of the injection is absorbed into the system but that this is unlikely to have any significant effects.

If a local anaesthetic is givenwith the steroid, the patient should be warned that this component ofthe injection may wear off after 2–4 h resulting in a temporary return of pain. Some advocate bed restor reduced activity for 12–24 h following injection into a large weight-bearing joint to improvetherapeutic benefit as injectedmaterial is cleared from the joint more rapidly with use of the joint [22].Chakravarty et al. have demonstrated a greater degree of clinical and serological improvement with24 h of hospital bed rest following knee injection [23]. However, two subsequent randomisedcontrolled found no advantage from resting after injection [24,25]. The constraints on bed capacity inmost rheumatology services result in the pragmatic advice for patients to rest as much as possible forthe first 24 h following the injection. Some rheumatologists providewritten information for the patientbut often this will not be read and understood until after the injection; hence, the discussion with thepatient remains very important.

Practice points on what to tell the patient

� Discomfort should be minor and short-lived.� Joint infection is extremely rare (comparable to sepsis after venepuncture).� Subcutaneous atrophy is a rare complication.� Flushing and post-injection pain may occur but settle spontaneously.� Minor systemic corticosteroid absorption occurs but is unlikely to be clinically significant.� The joint should be (relatively) rested for 24 h if possible after the injection.� Benefit is expected within 24 h, which may persist for 2 months or longer.� There is no evidence of damage to the joint from corticosteroid injection.



How do I know the needle is in the correct position?

The patient may experience some discomfort as the needle pierces the skin and joint capsule.Marked discomfort usually reflects inaccurate placement, for example direct contact with periosteum.A slight ‘give’ is usually felt as the needle enters the joint cavity but difficulty advancing the needlesuggests that it is in the wrong position. If there is marked resistance or discomfort, the syringe andneedle should be withdrawn slightly and gently advanced again after reassessment of the anatomicallandmarks. When the needle is correctly placed, the syringe should be pulled taking care not todislodge the needle. Aspiration of SF confirms correct placement. Correct placement is also suggestedby low resistance to injection. If the flow of SF becomes intermittent or stops, this may be due to

� temporary obstruction by synovial fronds,� blockage by fibrin and debris,� loculation of SF or� displacement of the needle outside the joint cavity.

If this happens, a small amount of fluid should be injected back in from the barrel of the syringe. Thisoften clears the needle of debris or overlying fronds permitting the aspiration to continue. Increasinguse of ultrasound, especially for technically challenging joints such as the hip, may aid accuracy ofinjections.

Practice points indicating correct placement of the needle

� Absence of severe discomfort� Lack of resistance to injection� Aspiration of SF

What benefit can be expected?

The aspiration of SF from a tensely swollen joint may quickly relieve pain by reducing intra-articularhypertension. In the absence of sepsis, the injection of a long-acting steroid into the joint may preventreaccumulation offluid and reduce synovial inflammation. The duration of benefit from steroid injectionoften starts within 24 h and usually persists for more than 2 months [19–23]. The clinical benefitassociated with IAC therapy has been shown by many uncontrolled studies [26–32] following the firstuse of such therapy in 1951 [26], although the extent of benefit differs considerably between studies.Blyth et al. reported the results of 300 adultswith RAwhowere evaluatedweekly for 12weeks followingIAC into the knee [29]. The authors showed that<40% of patients were pain free at 1weekwith a steadydecline in the percentage of patients who were pain free at 12 weeks. Padeh and Passwell reported theresults of IAC injection in71patientswith juvenile idiopathic arthritis inwhom82%of injections resultedin remissions of>6months duration [30]. The investigation of factors that may predict a good responseto intra-articular injection has been unhelpful [28,31]. None of the following correlatedwith the efficacyof IAC: disease duration, radiological scores, inflammatory markers and signs of inflammation. Patientswith inflammatory polyarthritis and more than two joints requiring injection may benefit more from achange in systemic disease-modifying therapy than multiple injections. A study of polyarticular IACinjection demonstrated better efficacy and less adverse effects than intramuscular corticosteroids [33];however, in practice multiple injections may not be well tolerated by some patients. Intra-articular in-jections in large and small joints have shown efficacy in early RA as part of a treat-to-target strategy [34].

Other intra-articular injectables

Osmic acid, yttrium and hyaluronic acid (HA) can also be given by intra-articular injection. Osmicacid synovectomy has been used as an alternative to surgery for chronic synovitis that is unresponsive


Practice points on benefits of IAC injection

� Aspiration of a tense effusion provides immediate relief.� Improvement after injection can be anticipated within 24 h.� The improvement may persist for 2 months or longer.� There are no proven predictors of maximal benefit.


to IAC [35], although much of the efficacy data for osmic acid comes from open studies and retro-spective series [36–41]. Initial remissionwith osmic acid is achieved in approximately half of the cases,with long-term remission in approximately 20% [40].

Yttrium synovectomy may also be considered when IAC treatment of chronic monoarticular sy-novitis fails [42–45]. Short-term efficacy is good but there are conflicting reports on long-term efficacyof yttrium [46–49].

HA is a high-molecular-weight polysaccharide that is a major component of SF and cartilage [50–52]. Despite an unclear mechanism of action, some randomised controlled trials report pain relief inknee OA fromvarious HA products, which is evident 2–5weeks after starting treatment andwhichmaypersist for several months [53–59]. However, because of cost, inconvenience and doubts concerning itsefficacy due to some negative trials, the clinical indications for HA are limited. Anti-tumour necrosisfactor (anti-TNF) alpha drugs have been administered by the intra-articular route with similar efficacyto corticosteroid injection [60], but their much greater cost will limit use.

What are the contraindications to joint injection?

There are very few contraindications to joint aspiration. Injecting through cellulitic or broken skinshould be avoided. Joints of patients who are anticoagulated may be aspirated and injected but moreprolonged pressure should be applied over the aspiration site and the procedure should be as atrau-matic as possible. The level of anticoagulation should ideally be within the therapeutic range. In pa-tients with suspected sepsis, it is imperative to aspirate the joint to make the diagnosis butcorticosteroid should not be injected if infection is suspected. Caution should be exercised if there isevidence of a localised staphylococcal infection such as a furuncle or suspicion of systemic infection.Corticosteroids should not be injected into a prosthetic joint without consulting an orthopaedic sur-geon. It is important tomake a diagnosis before injection as some conditions such as avascular necrosismay be exacerbated by IAC injection. Active tuberculosis, ocular herpes and acute psychosis have alsopreviously been considered as contraindications to steroid injection but cautious use may be consid-ered in specific circumstances.

Practice points

Contraindications to joint injection

� superficial infection or broken skin� unstable coagulopathy

Relative contraindication

� prosthetic joint

Key point

� Aspiration should be performed if sepsis is suspected.



Site-specific technique

Knee injection

The knee is the largest synovial joint and the easiest to aspirate. All major arthropathies may targetthe knee and it is the most common site for septic arthritis and pseudogout. The knee is therefore thecommonest site to require aspiration and injection. A knee effusion is first evident as a loss of themedialand lateral dimples around the patella. A large effusion represents a horseshoe swelling of the supra-patellar pouch above and to either side of the patella. There are several approaches to knee injection:

Medial approach

This is the preferred approach when there is relatively little fluid in the knee and for aspiration ofasymptomatic knees for diagnosis of gout or calcium pyrophosphate dihydrate (CPPD) crystal-associated arthritis (see below). The patient should rest on a couch with their whole leg supportedand relaxed. For smaller fluid collections that do not fully open up the suprapatellar reflection, a medialapproachmay be preferred. The site of entry is just below themid-point of the patella and the needle isaimed directly under the patella (Fig. 1). SF may be aspirated after as little as 1 cm of penetration and

Fig. 1. Medial approach to the knee.



deep introduction of the needle can be avoided. Pressure can be applied with the other hand toencourage fluid to the medial side. The injection is performed using a 19-gauge needle and 40 mg oftriamcinolone or equivalent.

Superolateral approach

A superolateral approach is commonly used for large effusions that distend the suprapatellar pouch.With a large tense effusion, the knee is most comfortable in mild flexion andmay require a soft supportunder the mildly flexed knee. The needle is introduced above and to the lateral side of the patella at themaximum convexity of the distended pouch, aiming downward and medially as if to go under theposterolateral aspect of the patella (Fig. 2). The distended pouch is superficial and the needle may notneed to be introduced far before SF is aspirated. The other hand should be used to tip the patellalaterally and encourage fluid to accumulate at the site of aspiration.

Popliteal cysts may be directly aspirated and injected by a posterior approach with ultrasoundguidance and there is some preliminary evidence of reduced size and reduced symptoms from the cystwhen compared to response of the cyst to conventional intra-articular injection [61].

Shoulder injection

Glenohumeral jointLimitation of external rotation is typical with glenohumeral problems. The glenohumeral joint can

be injected by an anterior or a posterior approach.

Anterior approach

The patient should place their forearm across the abdomen to partially internally rotate theshoulder. The point of entry is just inferolateral to the coracoid process (Fig. 3). SF may be aspirated inthe setting of inflammatory arthritis but with other shoulder lesions, especially adhesive capsulitis thefinding of fluid is unusual. The ease of injection should determine that the needle is in the right place ifno SF is obtained. The joint is injected using a 19-gauge needle and 40 mg of triamcinolone orequivalent.

Fig. 2. Superolateral aspiration of the knee. The examiner’s left hand is putting pressure on the medial suprapatellar pouch.


Fig. 3. Anterior approach to the glenohumeral joint.


Posterior approach

Identify the coracoid process anteriorly and the joint line posteriorly. The joint line can be identifiedif the patient is relaxed on the couch and the arm is rotated. Having marked the joint line, the injectionis pointing the needle towards the outer side of the coracoid process (Fig. 4).

Acromioclavicular joint

The acromioclavicular joint is a plane joint and can therefore be injected centrally from the front.The joint line is identified by palpation. The joint cavity is small and only accepts 0.5 ml of fluid. A fineneedle (23 gauge) is recommended with injection of 10 mg MPA or equivalent from a 2-ml syringe.

Fig. 4. Posterior approach to the glenohumeral joint.



Elbow joint

Anterolateral approachThe elbow joint may be involved in RA and other types of inflammatory arthritis. Fluid usually accu-

mulates earliest andmostprominentlyanteriorlyaround the radial head.With the patient’s elbow restingon a firm, comfortable surface and held flexed at 90�, palpate the radial head while passively supinatingand pronating the forearm. The joint line should be readily identified. Pass the 21-gauge needle towardsthe joint line froma superolateral angle (Fig. 5), aiming to place the tip justwithin the capsule, rather thandeep between the two bones. The injection is performed with 20 mg of triamcinolone or equivalent.

Wrist joint

The wrist is commonly involved in RA and other types of inflammatory arthritis including pseu-dogout. Swelling of wrist synovitis should not be confusedwith swelling of the extensor tendon sheath.The radiocarpal joint space should be identified by palpation, feeling for the triangular space betweenthe scaphoid and lunate in the centre of the distal radius (Fig. 6), and the injection is carried out whilstholding the wrist partially flexed. For the distal radioulnar joint, the injection is performed using asuperior approach just medial to the distal ulnar prominence with 20 mg of triamcinolone or equiv-alent via a 21-gauge needle. If the needle is in the correct position, it can be pushed easily to therequired depth and the injection can be made with little resistance.

First carpometacarpal joint

The pain of OA is the most common indication for local injection of this joint although the evidence ofefficacy is largely anecdotal [62]. The joint may also be involved in psoriatic arthritis and other inflam-matory arthritidies. The joint line should be identified by palpation and the injection performed from thelateral aspect near the abductor tendon using 10mg of MPA or equivalent via a 23-gauge needle (Fig. 7). Itis useful to distract the thumbwith the other handwhilemaking the injection to stretch the joint capsule.

Metacarpal and interphalangeal joints

These small-joint injections are most commonly performed for the management of RAor other inflammatory arthritis. If multiple small-joint injections seem to be required, then an

Fig. 5. Aspiration of elbow.


Fig. 6. A, Palpation of radiocarpal joint in mild flexion to identify the triangular space between the scaphoid, lunate and radius. B,Site of aspiration/injection of the radiocarpal joint.


increase in systemic disease-modifying therapy is generally advised in preference to multipleinjections.

The metacarpal joint line should be identified by gently flexing and extending the joint. The jointline is about 1 cm distal to the crest of the metacarpal head (Fig. 8). The injection is performed by asuperolateral approach using a 23-gauge needle to ensure that the neurovascular bundle is avoided.The patient should feel the joint being expanded by the injection and a maximum of 10 mg of MPA orequivalent should be used.

Similarly the proximal (Fig. 9) or distal interphalangeal joint line should again be identified bygently flexing and extending the joint. The superolateral approach avoids the neurovascular bundle,and a low volume only should be injected (2 mg MPA).

Ankle joint

With the foot in moderate plantar flexion, insert the 19-gauge needle in the space between the tibiaand the talus bounded medially by the tibialis anterior tendon and laterally by the extensor hallucislongus tendon (Fig. 10). It is important to direct the needle tangentially to the curve of the talus; themost commonmistake is to direct the needle toomuch towards the heel. Injection of the ankle is moreliable to be complicated by infection than other sites because of the tendency to oedema; hence, acareful aseptic technique is particularly important.

Subtalar joint

The subtalar joint is frequently involved in RA but often communicates with the ankle joint. The jointcan be injected using a lateral approach with the patient lying prone. The landmarks are a horizontalline drawn 2.5 cm above the distal end of the lateral malleolus and a vertical line 1.0 cm from theposterior border of the shaft of the fibula. The point where these lines cross marks the site of entry withthe needle pointed towards the proximal head of the first metatarsal. The injection should be givenwithout resistance using 20 mg triamcinolone or equivalent via a 21-gauge needle.


Fig. 7. Injection of the first carpometacarpal joint.


First MTP joint

This joint is classically associated with podagra but may be involved in RA, psoriatic arthritisor reactive arthritis. Examination of SF aspirated from this joint, even between attacks, may confirm thediagnosis of gout and IAC injection is an effective treatment for podagra. The joint line is identifiedby palpation, aided by slight flexion and distal distraction of the proximal phalanx, and the joint isentered superolaterally from the medial side, aiming under the extensor tendon, using a 23-gaugeneedle (Fig. 11). If aspirating an asymptomatic joint to confirm gout and an apparently dry tap isobtained, it is still worth emptying the syringe onto a slide – often a few drops of SF, sufficient forcrystal identification, are contained within the barrel of the needle. For IAC injection, use 4 mg MPA orequivalent.

MTP joints

MTP joints are commonly involved in RA and some cases of seronegative arthritis. Injection of thesejoints can be helpful particularly in early disease. The joint line is identified by gentle palpation and the23-gauge needle introduced obliquely under the extensor tendon. The injection should be performedwithout resistance using 10 mg MPA or equivalent.


Fig. 8. Approach to the (index) metacarpophalangeal joint.


Hip joint

The major indication for hip arthrocentesis is suspected infection. However, IAC injection has beenadvocated for the treatment of OA and inflammatory arthritis of the hip [63,64]. One double-blindrandomised trial [64] and some open studies [65,66] have suggested short-term benefit from IAC in-jection for hip OA, but the benefit was not sustained beyond 1–2 months. The use of imaging control isrecommended for aspiration or injection of the hip as arthrocentesis of the hip joint is technicallydifficult. Unless fluid is aspirated the needle cannot be confirmed in the joint space without the use ofimaging. Leopold et al. studied 15 human cadavers with 30 hip injections (15 anterior and 15 lateralapproach) of methylene blue dye without fluoroscopic guidance [67]. Anatomic dissections were doneon all specimens to determine the rate of success and the proximity of the needle to neurovascularstructures with each approach. Neither the anterior nor the lateral injection approach was sufficientlyreliable to recommend for clinical use without radiographic guidance.

Technique for hip arthrocentesis

The patient is positioned supine with the hip slightly flexed and internally rotated. The femoralartery and the inguinal ligament are identified by palpation. The skin and tissues down to the jointare infiltrated with local anaesthetic at the point of entry, which is lateral to the femoral artery and


Fig. 9. Approach to a proximal interphalangeal joint.


2 cm inferior to the inguinal ligament. The aspirating needle or trochar and cannula are insertedunder full aseptic precautions. If bone is encountered, the needle is withdrawn and inserted furtherlaterally towards the femoral neck as judged by the position of the greater trochanter. An alternativemethod is to pierce the skin more laterally at the level of the lower edge of the greater trochanterand point the needle inwards medially and upwards along the line of the femoral neck. The needlepath is adjusted (usually to a more shallow angle) until it passes through the capsule and the synovialmembrane.

With fluoroscopic control, the injection of a small amount of contrast material identifies the po-sition of the needle tip. With ultrasonography, the hip joint is identified andmarked in the longitudinaland transverse planes. The needle is inserted where the two lines cross, and the position of the needletip can be confirmed on scanning.

Sacroiliac joint

The sacroiliac (SI) joint is relatively inaccessible and requires imagingwhen aspiration or injection isattempted. This is best done under computed tomography (CT) fluoroscopy or magnetic resonanceimaging (MRI) usually by an experienced radiologist or orthopaedic surgeon [68,69]. The major indi-cation for arthrocentesis of the SI joint is suspected sepsis (unilateral presentationwith fever, systemicupset and elevated C-reactive protein (CRP)). There are conflicting reports regarding the efficacy of SI-


Fig. 10. (A) Palpation of the space between the tibialis anterior and extensor hallucis longus. (B) Approach to the ankle joint.


joint injectionwith long-acting corticosteroids in the management of inflammatory sacroiliitis [68,70].There may be some merit in considering IAC injection of the SI joint if maximal oral and physicaltherapy have failed to provide adequate relief of symptoms.

Apophyseal joints

Interapophyseal (facet) joint injections were first reported byMooney and Robertsonwith a successrate of 52% [71]. However, controlled studies using corticosteroid and local anaesthetic injectionshowed no benefit over saline [72,73]. Dolan et al. showed that single-photon emission computedtomography (SPECT) scanning can identify back pain sufferers likely to obtain short-term benefit fromfacet joint injections [74]. This study showed that clinical examination alone may be unreliable as facetjoints are innervated from branches to the posterior primary ramus at the corresponding level andfrom the nerve root above. The technique should only be performed under imaging control by anexperienced radiologist or anaesthetist.

Practice points on sites of injection

� The hip, SI and interapophyseal joints should be approached under imaging control.� The preferred approach to the joint may depend upon individual patient circumstances.

Research agenda

� Appropriately powered prospective studies may identify the factors predicting a betterresponse to IAC injection at specific joints with specific diagnoses.

� The merits of intra-articular hip, SI and apophyseal joint injections should be determined byappropriately powered, randomised, placebo-controlled trials.


Fig. 11. Approach for the first metatarsophalangeal joint.


Summary

Joint aspiration/injection is an invaluable and safe procedure for the diagnosis and treatment ofjoint disease. Joint aspiration provides important diagnostic information on septic arthritis and crystalarthritis. Intra-articular injection of long-acting insoluble corticosteroids produces rapid resolution ofinflammation in most injected joints. Making a correct diagnosis before undertaking an intra-articularinjection and explaining the technique to the patient are crucial. Provided simple aseptic precautionsare taken, joint injection is a safe and well-tolerated procedure. Most peripheral joints are readilyaccessible to an experienced clinician but other joints (hip, SI and interapophyseal joints) requireimaging assistance. More information regarding the efficacy of corticosteroid injection at these andother individual sites such as the first carpometacarpal joint would be welcome. In conclusion, IACinjection is an important adjunct to the management of inflammatory arthritis and OA, providingworthwhile and often dramatic benefit for localised symptoms.

Synovial fluid analysis

The joint cavity is delineated by the two articulating surfaces of hyaline cartilage and by the periph-erally located synovium. The synovial membrane has no basal layer or epithelial cells [75] but contains a



rich vascular net. Themore superficial capillaries close to the lining cells are fenestrated, facilitating rapidchanges in water and solutes and supporting an active physiological role for the membrane.

All diarthrodial joints contain minute amounts of SF in their cavity. Paracelso (1493–1541) namedthis fluid ‘synovial’ because of its similarity to egg white in being clear yellow, transparent and viscous[76]. SF originates from the plasma that is filtered by the capillary net and diffuses into the joint cavity,with the addition of locally synthesised HA, which gives SF its characteristic viscosity [77]. The synovialmembrane also lines the inner aspect of tendon sheaths and synovial bursae. The function of the sy-novial membrane and SF includes the transport of nutrients to the avascular joint cartilage, assistancein joint lubrication and joint ‘cleaning’ and defence. Approximately 0.5 ml of SF can be obtained byaspiration of a normal knee (Fig. 12), with only a drop or two coming from a clinically normal first MTPJ[1], but in joint disease the volume of SF generally increases, making aspiration technically easier.

Joint inflammation and SF

Essentially two types of conditions affect joints: inflammatory and non-inflammatory (mostcommonly OA). Although inflammation targets the synovial membrane, some cellular elements ofinflammation cross into the joint cavity and can be detected in SF. In some non-inflammatory condi-tions, the increased SF volume appears to originate from dilated capillaries adjacent to altered jointstructures, suggesting a primary role for mechanical factors [78]. In most instances, the macroscopicappearance of aspirated SF permits distinction between inflamed and uninflammed joints and mayalso provide additional diagnostic information.

Macroscopic appearance

The appearance of aspirated SF is evident at the bedside, providing immediate information [79,80].In general, the more a joint is inflamed the greater the SF volume, the higher the cell count and sub-sequent turbidity, and the lower the viscosity (Fig. 13). ‘Non-inflammatory’ SF has very few cells and

Fig. 12. Synovial fluid aspirated from a normal knee - small volume of clear, slightly yellow, highly viscous fluid.


Fig. 13. Range of naked eye appearances of synovial fluids: non-inflammatory SF (A); inflammatory SF (B); and pyarthrosis(C).


looks transparent. Plastic syringes are not always totally clear and it may be helpful to transfer the SF toa clear glass or plastic tube to distinguish transparent from slightly turbid SF. Sometimes small frag-ments of synovial membrane, cartilage or fibrous tissuemay be seen as faint floating debris within suchtransparent SF. SF from markedly inflamed joints (e.g., pyogenic infection, active RA and acute crystalsynovitis) have the highest cell counts and turbidity and may even appear as frank yellow–green pus(Fig. 13). Although such ‘pyo-arthrosis’ should always lead to consideration of sepsis, it is not specificfor this diagnosis. Slight turbidity can result from red as well as white cells and microscopic exami-nation of the SF may be needed to determine the cell type. Large numbers of red cells give theappearance of haemarthrosis (Fig. 14), which can be caused by a generalised bleeding diathesis (e.g.,overcoagulation and haemophilia), joint trauma or synovial tumours (e.g., pigmented villonodularsynovitis) but more commonly by aggressive synovitis (e.g., sepsis, RA and crystal synovitis) or internalderangement. The combination of haemarthrosis topped by a layer of glistening pale yellow fat isdiagnostic of a subchondral fracture (the lighter fat deriving from subchondral bone).

Occasionally particles other than cells contribute to the turbidity and colour of SF. For example, amilky-white SF can result from the presence of a high concentration of

� monosodium urate (MSU) crystals,� CPPD crystals; and� basic calcium phosphates, mainly carbonate-substituted hydroxyapatite.

Cholesterol crystals may also give a yellow-to-creamy appearance. Metal wear particles from jointprostheses may give a greyish hue [81] and fragments of ochronotic cartilage [82] can give a ‘salt andpepper’ appearance. In RA and other inflammatory arthropathies, fibrin shreds may contribute to SFturbidity and mislead the observer with respect to the degree of joint inflammation [83]. It is wise toroutinely check SF samples under the microscope to determine the precise cause of SF turbidity.

Differential cell counts and cytology

In general the percentage of polymorphonuclear (PMN) leucocytes in SF broadly equates to the de-gree of inflammation, but due to considerable variation between patients its diagnostic value is limited.

Effusions containing only mononuclear cells have been described in some viral arthritides and inearly RA. A predominance of eosinophils may be seen in parasitic arthritides, hypereosinophilic


Fig. 14. (A) Haemarthrosis and (B) blood tinged synovial fluid, reflecting trauma at the time of needle insertion.


syndrome and other hypereosinophilic conditions [84]. Malignant cells have been identified intumoural or metastatic joint disease and leukaemia cells may be seen in SF. Bone marrow cells may beidentified following intra-articular fracture. Lupus erythematosus (LE) cells and haematoxophilicbodies can be seen rarely in lupus arthropathy. Reiter cells can be identified in some inflammatory SF[85] but have little diagnostic specificity.

SF and infection

When an infection is suspected, appropriate stains and cultures should be carried out depending onthe growth requirements of the different possible organisms. SF taken into blood-culture bottles ratherthan just sterile universal containers increases the detection rate, especially for Gram-negative or-ganisms. Where clinical suspicion of infection is high, antibiotic treatment should be commenced oncesamples are obtained and not delayed to wait for results. High levels of lactic acid and low levels ofglucose in an SF sample are suggestive but not specific for septic arthritis but these tests are rarelyundertaken in practice [86–88].

Analysis of crystals

Identification of MSU crystals in SF or in an aspirate of a tophus is considered the gold standard fordefinitive diagnosis of gout [89]. Similarly the finding of CPPD crystals in SF is diagnostic of CPPD-associated arthropathy [90]. MSU and CPPD crystals can be identified in SF aspirated from jointsduring acute attacks of gout or pseudogout and also from more chronically inflamed joints. They mayalso be identified in SF aspirated from an intercritical, asymptomatic and clinically un-inflamed joint,and even from an asymptomatic knee or first MTPJ that has not previously been affected by an acute



attack [91–94]. Although it is common practice to diagnose typical presentations of both conditionsprimarily on clinical grounds alone, it is best to confirm the diagnosis by SF crystal identification,especially in atypical cases. Imaging with ultrasonography can give helpful diagnostic information(‘double contour sign’) [95] but the definitive diagnosis still relies on crystal identification. Examinationof SF for crystals is advised also for any undiagnosed inflammatory arthritis in an adult and crystals maybe found in patients with an alternative prior diagnosis [96]. For untreated gout, aspiration of the firstMTPJ with a 29-gauge needle permits definite MSU identification in over 90% of cases [1,97].

Since its introduction by McCarty and Hollander, the standard instrument for routine identificationof MSU and CPPD crystals in SF has been the polarised light microscope equipped with a first-order redcompensator. Apatite crystals are too small to be seen by light microscopy although the use of calciumstains (mainly for research purposes) permits visualisation of aggregates of apatite in SF. Crystals otherthan MSU or CPPD are rarely identified.

Most studies report low inter-observer reliability for detection of MSU and CPPD in SF, particularlyfor CPPD crystals [98,99]. In two such studies, SF samples were divided and sent to laboratories thatroutinely report on SF crystals [100,101]; in a third, cytocentrifuge slides were distributed [98,102]; andin a fourth the search was carried out using Gram-stained slides [103]. Artificial MSU and CPPD crystalshave also been used in reliability studies [104]. However, none of these studies reflect microscopyundertaken in the optimal setting: that is, analysis of fresh SF by properly trained, expert observerswho are blind to clinical details. Lumbreras et al. have shown that observer training results in veryacceptable consistency in the identification of both MSU and CPPD crystals, although CPPD remain themost difficult to identify [105]. It therefore appears that any problems in SF crystal identification relatemore to training than to the technique itself. The search for crystals is best done in fresh SF where cellintegrity is well preserved. This is particularly important for CPPD crystals, which are often intracel-lular. Nevertheless, both CPPD and MSU crystals can still be readily identified after 24 h in refrigeratedor even frozen SF samples [106].

One problem with CPPD crystal identification is overdependence on birefringence as the meansof identification. All MSU crystals are strongly birefringent and are clearly distinguished by meansof compensated polarised light microscopy (CPLM). However, CPPD crystals are only weakly bire-fringent. In one study, in which CPPD crystals in SF were first identified using ordinary light andthen examined using polarised filters, only 20% of CPPD crystals showed sufficient birefringence tobe identified as birefringent [107]. Thus, using CPLM alone, only one in five CPPD crystals will beidentified as weakly birefringent crystals compared to the much higher detection rate for brightlybirefringent MSU. In the first seminal description of SF CPPD crystals, McCarty et al. noted this weakbirefringence and used phase-contrast microscopy in addition to CPLM to increase the sensitivityfor detection [108]; this combination remains the standard for searching for crystals (Figs. 15 and16) [109]. This weak and occasionally absent birefringence of CPPD has been noted by others[110,111]. Importantly, however, both MSU and CPPD crystals can be distinguished by theirmorphological characteristics alone using ordinary light microscopy [112]. To avoid missing crystals,especially CPPD, a two-step procedure for SF crystal analysis is recommended, at least during thetraining phase [105]:

1. Crystal detection: to determine whether crystals are present; and2. Crystal identification: inwhich any identified crystals are correctly assigned as MSU, CPPD or some

other crystal.

The initial crystal-detection step is carried out first under ordinary light, to identify crystals by theirgeometric, sharp line morphology (this shows CPPD crystals well), then under plain polarised light (nocompensator) to identify crystals by birefringence (this readily detects MSU crystals) (Figs. 17 and 18).In general, �400 magnification is adequate. However, especially during training, observation underordinary light at �1000 using an oil immersion lens helps familiarise the observer to polymorphic(rhomboidal, parallelepipedic and needle-shaped) CPPD crystals (Fig. 19). Many CPPD crystals areintracellular, even in SF from un-inflamed joints [96,113]. The intracellular position of crystals in freshSF helps to confirm that theywere aspirated from the joint and are not artefacts. CPPD crystals are oftenvery small and within cells may appear as small squares or needles or even as inclusions but with a


Fig. 15. Monosodium urate (MSU) crystal and cells seen using a phase light microscope (magnification 400).


linear border or angle. Such inconclusive findings should prompt a further search until larger, moretypical-looking crystals are found. Under uncompensated polarised light, all MSU crystals show strongbirefringence and appear as bright, shiningwhite objects against the dark background.Most, but not allMSU crystals are needle-shaped. When crystals are strongly suspected but not seen in an SF sample,the detection rate may be increased by centrifugation and a repeat search instituted in the pellet wherecrystals concentrate along with cells and fibrin debris. In apparently crystal-negative SF fromOA joints,submicroscopic CPPD crystals may be identified by analytical electron microscopy [114].

In the crystal-identification step, CPLM essentially permits distinction betweenMSU and CPPD crystals.MSU crystals show strong negative birefringence and are bright yellow when parallel to the axis of thecompensator and bright bluewhenperpendicular to it (Fig. 20). By contrast, CPPD crystals showonlyweakpositive birefringence, appearing pale yellowwhen their long axis is perpendicular to the compensator andpale bluewhenparallel (Fig. 21). The large number of CPPD crystals that showno birefringence under plainpolarised light may show very faint or no colour under CPLM. Keeping a reference slide with MSU crystals

Fig. 16. Tiny calcium pyrophosphate dihydrate (CPPD) crystal seen using a phase light microscope (magnification 1000). This mi-croscope allows a good visualisation of the crystal shape and can be very helpful in crystal detection and the identification ofverysmall crystals of CPPD.


Fig. 17. Monosodium urate (MSU) crystals (uncompensated polarised microscope, magnification 400).


(easily obtained from a tophus) is useful for confirming the axis of the compensator. CPLM is particularlyuseful when SF contains both CPPD and MSU crystals and when other potentially confusing crystals arepresent, such as needle-shaped cholesterol or corticosteroid crystals.

In patients with tophi, material with crystals can be obtained by puncture with a syringe fitted witha simple intramuscular needle; the white thick material usually stays inside the needle. CPLM willshow that the sample is composed almost exclusively of tightly arrangedmasses of MSU crystals, oftenwith tissue or cellular debris (Fig. 22).

Some tips for the beginner

Buying the microscope

Manufacturers and retailers may encourage you to buy multifunctional polarised microscopes usedby geologists. Although excellent, these can be expensive and unnecessarily sophisticated. For routine

Fig. 18. Abundant monosodium urate (MSU) crystals (uncompensated polarised microscope, magnification 1000).


Fig. 19. (a) Calcium pyrophosphate dihydrate (CPPD) crystals. Note the small rhomboidal and large needleshaped crystals (ordinarylight, magnification 1000). (b) Same field as shown in (a) but here seen using polarised filters, without a first order red compensator.Note that the large needle-shaped crystal does not show birefringence and could have passed unnoticed if the search had beenconducted with polarised light only (magnification 1000).


clinical use, a simple light microscope (with �100, �400 and �1000 oil immersion) fitted withpolarised filters and a first-order red compensator should suffice. These are produced by many man-ufacturers and are much cheaper.

Acquiring familiarity with the crystals

To the experienced observer, CPPD andMSU crystals look very different and are easily distinguishedby shape alone. It is important to become familiar with MSU and CPPD crystals and also with artefacts.To do so it helps to spend time looking under both ordinary and polarised light at SF samples obtainedfrom diagnosed patients.

Fig. 20. Monosodium urate (MSU) crystals seen using a polarised microscope fitted with a first order red compensator. The crystalparallel to the axis of the compensator shows bright yellow while the one perpendicular to the axis is bright blue (magnification400).


Fig. 21. Calcium pyrophosphate dihydrate (CPPD) crystal seen using a polarised microscope fitted with a first order red compen-sator. The axis of the compensator is parallel to the longer axis of the crystal, which shows a blue colour (magnification 1000).


Artefacts and non-crystalline material

Artefacts such as dust, hairs, glass fragments and talc powder are common causes of confusion forbeginners. Letting a glass slide stand overnight on the bench and examining it using the polarisedmicroscope will often reveal large amounts of birefringent particulate contaminants. With practice,most artefacts soon became evident, being suggested by one or more of the following: lack of geo-metric shape, very large or very small size or mixed birefringence. Small ‘beach-balls’ or Maltesecrosses raise consideration of calcium oxalate crystals (see below) but are more commonly caused bydust or talc (Fig. 23). Cartilage fragments are commonly observed in SF, even from normal joints, andappear as irregular-shaped translucent particles of varying size (Fig. 24).

Fig. 22. Aspirate from a tophus viewed under low power (x100) CPLM, showing a mass of brightly birefringent needle-shapedcrystals and tissue debris.


Fig. 23. A single Maltese cross (CPLM x400) - a nonspecific appearance that can result from calcium oxalate crystals but also fromartefacts such as talc or dust.


Apatite crystals

Apatite and other basic calcium phosphate crystals [115] have been noted in SF in rapidlydestructive forms of OA [116,117], acute monoartritis [118,119], systemic sclerosis and dermatomyositis[120], advanced OA [121,122] and RA [123,124]. In general they appear more abundant in joints withadvanced damage [124], suggesting that their origin may be from subchondral bone (apatite and basiccalcium phosphates are the normal mineral components of bone). Thus, SF apatite is a non-specificfinding that can occur in a wide range of arthropathies [124,125]. Apatite crystals are too small to beseen by light microscopy and appreciation of individual crystals requires electron microscopy.Electron-probe analysis allows determination of the relative amounts of the crystal componentswhereas the X-ray diffraction pattern allows definitive identification. Alizarin Red S stain, a non-

Fig. 24. Cartilage fragment in synovial fluid viewed under ordinary light x400, showing lack of geometric straight lines or angles andtranslucent appearance.


Fig. 25. Apatite aggregates stained with alizarin red at acidic pH under ordinary light x400.


specific stain for calcium salts, has been proposed as a means of detecting apatite-crystal aggregates(Fig. 25) [126]. However, it is only positive in SFwith high concentrations of crystals, and other calcium-containing crystals, including CPPD, may also give positive Alizarin Red staining [124]. The specificityfor apatite is increased if the stain is used at acidic pH. Oxytetracycline stainingmay prove to be a usefuladjunct to available methods [127] but at present, largely because of its lack of disease specificity and

Fig. 26. Large cholesterol crystals (CPLM x400) showing flat envelope appearance, deleted corners and bright mixed birefringence.


Fig. 27. Corticosteroid crystals (CPLM x400) showing rounded contour with no sharp angles.


technical difficulties related to its detection, investigation for apatite and other basic calcium phos-phates in SF has little clinical utility and is largely reserved for research.

Calcium oxalate crystals

Calcium oxalate crystals have been identified in SF from joints of patients undergoing periodichaemodialysis and also in those with hyperoxalaemia and oxalosis. Although the irregular shape ofmany of the crystals does not allow morphological identification, a few have a characteristic bipyra-midal or ‘Maltese cross’ shape [128]. Being a calcium salt, oxalate crystals also stain with Alizarin Red.Oxalate arthropathy was largely eliminated by modifying filter systems during haemodialysis andexcept in this setting the investigation of these crystals has little clinical relevance.

Cholesterol crystals

These are occasionally found in SF from chronic, largely inflammatory effusions [129–133]. Theirpathogenic potential appears to be small, although in some animal models cholesterol crystals producegranulomata, synovial cell hyperplasia and fibrosis [123]. Cholesterol crystals appear as extremely largerhomboidal plates, often with a broken or folded-over corner and showing bright, mixed birefringence(Fig. 26) [17,115].

Corticosteroid crystals

A post-injection flare following IAC injection may simulate an infection and lead to a diagnosticjoint aspiration [134]. Often in this setting, birefringent crystalline particles of steroid can be seen in SFfor some time following their injection (Fig. 27). Different preparations have different microscopicappearances [135], but none should cause confusion with MSU or CPPD.

Other crystals

Much of the information on other crystals is anecdotal. SF lipid crystals, round inclusions that showa birefringent Maltese cross under CPLM, have been described in acute arthritis [136] and can be seenin the arthropathy associated with pancreatic disease [137] and in joints with intra-articular fracture[138]. Charcot–Leyden crystals have been noted in eosinophillic synovitis [84].


Research agenda

� In general, data on themore basic procedures of SF analysis, such as the gross appearance, theusefulness of cellularity and the percentage of PMN leucocytes, are based on opinion andanecdotal information. Formal critical evaluation would be useful.

� CPPD crystals are more difficult to identify in SF than MSU crystals. Study of the comparativeability to detect CPPD crystals in SF by means of a light microscope, a polarised microscopeand a phase microscope would be welcomed.

� Gout and CPPD-related arthropathy are often diagnosed on clinical grounds alone. An eval-uation and analysis of the crystal yield in undiagnosed ‘less typical’ arthropathies would bevery useful.

Practice points

Macroscopic appearance and cell count:

� The macroscopic appearance of SF often provides immediate information about the degree ofinflammation present in a joint and may also provide other diagnostic information.

� The total number and percentage of PMN leucocytes tends to be higher in more inflammatoryprocesses, but this is non-specific.

SF from joints with infections:

� Appropriate microbiological cultures are the essential diagnostic tool in the identification ofinfection.

Crystal detection and identification:

� Only about one in five CPPD crystals show birefringence when observed using a polarisedmicroscope: their initial detection is better carried out with an ordinary microscope.

� By contrast, almost all MSU crystals are strongly birefringent under uncompensated polarisedlight and are easily identified using this method.

� MSU and CPPD crystals are regularly found in asymptomatic joints of patients with gout andCPPD-related arthropathy, permitting confirmation of the diagnosis of crystal depositionduring the intercritical period.

� Crystal deposition and sepsis may co-exist; hence, despite the presence of crystals SF shouldbe cultured if sepsis is suspected clinically.

� CPPD and MSU crystals should be searched for in all undiagnosed joint effusions.


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Joint aspiration and injection and synovial fluid analysis...Joint aspiration and injection and...

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