Examination General Always compare sides. Establish whether there is true synovial swelling . A history of swelling is not always reliable. Enthesial in \202 ammation in SpA does not usually cause swelling. Affected joints Examine for tenderness. Check the range of (passive) movement, for locking and instability. \200 Acute processes, such as crystal arthritis and infection often lead to a painful swelling, marked tenderness of swollen soft-tissues, and painfully restricted active and passive move ment of the joint. Features are usually less overt with chronic arthritis. Instability of a n acutely in \202 amed joint or tests for carti- lage damage in the knee may be dif \201 cult to demonstrate. Further examination will be necessary after drainage of joint \202 u id/haemarthrosis. Detection of enthesis tenderness around the affected joints or at other s ites is a useful clue to the underlying diagnosis of SpA. Family and social history There may be important clues from the family and social history. PATTERNS OF RHEUMATOLOGICAL DISEASE: OLIGOARTICULAR PAINS IN ADULTS 16 Lipid and cholesterol crystals are not uncommon in joint \202 uid samples, but their sign i \201 cance is unknown. Crystals seen less commonly, but in typical settings include hydr oxyapatite associated with Milwaukee shoul- der (or knee) syndrome (alizarin red-S stain po sitive), calcium oxalate in dialysis patients (may need scanning electron microscopy), cyst ine in cystinosis, and xanthine in xanthinosis. The presence of crystals in joint \202 ui d does not exclude infection. The commonest causes of non-gonococcal septic arthritis in Eu rope and North America are Staph aureus (40 \200\22350%), Staph epidermidis (10 \200\22315% ), Strep species (20%), and Gram-negative bacteria (15%). Examination of other musculoskeletal structures \200 Examine the back and for sites of bony tenderness. Sacroiliitis and enthesitis are common i n SpA. Tendonitis is not speci \201 c and can often occur in gout, CPPDD arthritis, SpA, a nd gonococcal infection. Skin rashes and other features of in \202 ammation Oligoarthritis may be part of a systemi c in \202 ammatory/ infective condition. \200 Temperature and tachycardia can occur with non-infective causes of acute arthritis (e.g. cr ystal arthritis), although their presence with oligoarticular joint swelling requires exclu sion of joint infection. Gouty tophi may be seen in the pinnae, but also any- where periphe rally. They can be dif \201 cult to discriminate clinically from rheumatoid nodules. Polar ized light micro- scopy (PLM) of material obtained by needle aspiration will be diagnostic for tophi. The hallmark of relapsing polychondritis is lobe-sparing, full thickness in \202 ammation of the pinna. Mouth ulcers can occur with any illness; however, crops of larg e painful lesions associated with oligo-articular arthritis suggests Beh et \200\231s dise ase. A typical site for osteitis associated with axial sarcoid or SAPHO (Le Syndrome, Acn , Pustulose, Hyperostose et Osteit ) is manubriosternal. Erythema over a joint suggests cr ystal or infection. Associated skin rashes may include erythema nodosum (associated with an kle pains in sarcoid), the purpuric pustular rashes of Beh et \200\231s, gonococcal infect ion (single pustules) and Le SAPHO, erythema marginatum (rheu- matic fever), or keratoderma blenhorragica (aggressive- looking psoriasis-like rash of the sole of the foot in reactive arthritis disease). Psoriasis may be associated with synovitis, enthesitis or periostitis. Table 1.5 Features of joint \202 uid Feature Normal Non- In \202 ammatory Septic in \202 ammatory Viscosity V high High Low Varies Color None Straw Straw Varies + orgs Clarity Clear Clear Opaque Opaque 200 200 \200\2232000 2000 \200\22350 000 >50 000 Leucocytes (cells/mm3) \200 PMNs (%) <25 25 Often >50 >75 Radiographs Radiographs can con \201 rm an effusion, show characteristic patterns of chond ral and bone destruction (e.g. in infection or erosive gout), and show intra-articular calc i \201 cation from CPPDD or hydroxyapatite. \200 If septic arthritis is suspected radiographs are essential. Patchy osteopaenia and loss of bone cortex are cardinal signs. Punched-out (Lulworth Cove) erosions, soft tissue swellings (tophi) and patchy calci \201 cation are hallmarks of chronic gout. Intra-articular calci \201 cation may be either chondrocalci- nosis ( \201 ne linear or punctate \201 brocar tilage calci \201 cation) or larger loose bodies (often with osteophytes). Both associate with CPPDD arthritis. Numerous round-shaped calci \201 c masses in a joint can be due to s ynovial chondromatosis (commonest in middle- aged men, 50% of cases \200\223 knee). The pr esence of erosions per se does not imply RA. Erosions can be due to erosive enthesitis asso ciated with SpA, CPPDD arthritis, and gout. Investigations Doubt about the presence of synovitis can be addressed by obtaining US or ma gnetic resonance (MR) imaging of the joint(s) in question. Joint aspiration (see Table 1.5) Fluid should be sent in sterile bottles for microscopy and culture. \200 Synovial \202 uid appearances are not speci \201 c. Blood or blood-staining suggests hae marthrosis from trauma (including the aspiration attempt), haemangioma, PVNS, synovioma, or occasionally CPPDD arthritis. Turbidity of \202 uid relates to cellular, crystal, lipid, and \201 brinous content, and is typical in septic arthritis and acute crystal arthritis owing to the number of polymor- phonuclear (PMN) leucocytes. Cell counts give some diagnos tic guidance, but are non-speci \201 c. There is a high probability of infection or gout i f the PMN differential is >90%. Joint \202 uid eosinophilia is not speci \201 c. Compens ated PLM of fluid can discriminate urate (3 \200\22320 m, needle-shaped, negatively biref ringent \200\223 blue and then yellow as the red plate compensator is rotated 90 ) and ca lcium-containing crystals, e.g. CPPDD (posi- tively birefringent, typically small, and rect angular or rhomboid in shape). MR Further MR imaging should be discussed with your radiologists. \200 Confirmation of traumatized structures, such as meniscus damage in the knee and labral dama ge in the shoulder should be sought if suspected. MR can con \201 rm synovitis, although a ppearances are usually non-speci \201 c. Focal high signal in bone on T2 and fat suppresse d images ( \200\230bone bruising \200\231) if in sub-enthesial sites can indicate osteitis in SpA. \200 CHAPTER 1 Clinical assessment of rheumatological disease 17 Serum angiotensin converting enzyme (sACE) (occurs in, although is not speci \201 c for, s arcoid), IgM Borellia burg- dorferi serology (acute arthritis or history of migratory arthr itis in Lyme disease). Antibodies to the streptococcal antigens streptolysin O (ASOT) DNAas e B, hyaluronidase, and streptozyme in patients who have had sore throat, migratory arthrit is or features of rheumatic fever. Ultrasound Many rheumatologists use US to aid diagnosis and characterize in \202 ammatory arthritis in the clinic. \200 Joint and tendon thickening, and changes in appearance of soft-tissues are all identi \201 able with US. US is more sensitive than clinical examination and radiographs at detecting small joint synovitis in RA. The addition of patterns of abnormality with Doppler is useful in assessing the activity of synovitis in joints in RA and in \202 ammatory arthritis. Er osions at small joints are detectable in patients with in \202 ammatory arthritis at an ea rlier stage compared with radiographs. At the wrist US can also show features suggestive of median nerve entrapment. In experienced hands US can be used to show clinical and asymptom atic entheseal changes around the hind- foot in SpA patients. Ultrasound-guided glucocortic oid injections into differ- ent structures (including sub-acromial space) has been shown to be more accurate than bedside injection without imaging. Synovial biopsy \200 If there is a haemarthrosis or suspicion of PVNS, MR of the joint is necessary before under taking a biopsy to characterize the vascularity of a lesion. Consider a biopsy in the follo wing situations: undiag- nosed monoarthritis, suspicion of: sarcoid arthropathy, infection despite negative synovial fluid microscopy and cultures, gout despite failure to detect cry stals in synovial \202 uid and amyloid. Formalin \201 xation of samples is suf \201 ci ent in most cases. Samples for PLM are \201 xed in alcohol (urate is dissolved out by for malin). Snap freezing in nitrogen is essential if immunohistochemistry is required. Arthros copic biopsy will yield more tissue than needle biopsy; it may add diagnostic information a nd joint irriga- tion can be undertaken. Congo red staining of synovium, ideally with PLM, should be requested if AA, AL or \2372-microglobulin amy- loid is a possibility. Typical s ituations are in myeloma (AL) and long-term dialysis patients ( \2372-microglobulin). AA am yloid (in long-standing RA, AS, FMF and Crohn \200\231s disease) is a rare, although recogn ized complication of each condition. Laboratory investigations to consider \200 Full blood count (FBC), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP). Neu trophilia is not speci \201 c for infection and can occur in crystal arthritis. Blood urea , electrolytes, creatinine and urate (e.g. hype- ruricaemia and renal impairment with gout) . Blood calcium, phosphate, albumin, ALP [ parathyroid hormone (PTH)], thyroid function t ests, and ferritin to screen for hyperparathyroid or thyroid disease or haemochromatosis as sociated with CPPDD arthritis. Autoantibodies: rheumatoid factor (RF) is not speci \201 c for RA. Cyclic citrullinated peptide (CCP) antibodies are probably more sensitive for a dia gnosis of RA in early in \202 ammatory arthritis patients. However, acuity of \201 nd- i ngs is still likely to be blunted by suboptimal case ascer- tainment. Low titre CCP antibod ies do occur in non-RA in \202 ammatory arthritides. WIDESPREAD PAIN (IN ADULTS) K. HARRIS 18 Widespread pain (in adults) Many conditions are characterized by musculoskeletal symptoms, some of which may be diffuse or multicentric. Also, the interpretation and reporting of symptoms varies and can be a so urce of confusion. Widespread pain due to bone pathology alone should be considered. Bony pain is often unremi tting, day and night. It changes little with changes in posture and movement. Discriminatin g whether there is a single process causing the widespread pain may depend on whether the s ame types of lesions are consistently present. Are all symp- toms only from joints? Is ther e a combination of enthe- sial and joint pains? Problems may arise if it is assumed that al l pains arise from a single pathological process. In children and young adults this would b e likely, but in the elderly, particularly where there is late presentation, multiple patho logies are often present. Background History: general points Widespread symptoms can be due a variety of conditions, not all affecting joints. Assessment requires consideration of disease characterized by: \200 Polyarticular disorders such as RA, prostate speci \201 c antigens (PSA), and CPPDD polyar thritis. Conditions of muscle [e.g. polymyositis, polymyalgia (PMR), sarcoid, statin-induce d myalgia]. Polyenthesopathies primarily psoriasis-associated but also enteropathic SpA, SA PHO, and sarcoid. Pain from a combination of muscle, joint, and tendon complicated by fatig ue (e.g. SLE, Sjogren \200\231s). Neurological disease, such as cervical myelopathy (mimick ing musculoskeletal \200\223 \200\230stiffness \200\231) and in \202 amma- tory dural di sease (e.g. \200\230burning pain \200\231 dysaesthesia in neurosarcoid). Chronic pain ampl i \201 cation and fatigue. Establish which joints are affected \200 A symmetrical pattern of small joint synovitis is typical of, but not speci \201 c for, RA . Chronic arthritis from parvo- virus B19 infection, pseudo-rheumatoid PSA, polyarticu- lar gout (particularly in postmenopausal women) and CPPDD polyarthritis in the elderly may mim ic RA in this respect. Small hand joint pain occurs in nodal generalized OA and PSA. PIPJ a nd thumb CMC joints can be affected in both. PSA patients often have additional enthesitis and in \202 ammatory lesions in feet. The latter would be more unusual in OA. The combinat ion of sacroiliac pelvic and lower limb joint/enthesis pain, typically in an asymmetrical o ligoar- ticular pattern, is suggestive of SpA. Large and medium-sized joints are typically affected in CPPDD disease, but a picture of multiple joint involve- ment similar to that in RA is possible (including tenosynovitis). CPPDD disease can affect spinal structures. Wide spread arthralgia/arthritis occurs in patients with leukaemias, lymphoma, and myeloma, and with certain infections (see Table 1.6). Lesions may be a complex combination of involving joint, muscle, and bone. Examination: general points Assessment needs to be comprehensive if joint disease is not ev ident on examination. Full neurological examination is often necessary. \200 An appreciation of the distribution of lesions likely with polyenthesopathy, the neurologic al signs of neuromenin- geal sarcoid and distribution of fibromyalgia tender points is impo rtant. Slowly evolving myelopathy can result in few hard signs. The \200\230flavor \200 \231 of increased tone in limbs, generalized increase in re \202 exes and blunted skin sen sation to \201 ne pin- prick or light touch in the legs is often all that is detected. \200 History Age, gender, and racial background The degree to which these factors in \202 uence the likelihood of disease varies according to the background disease occurrence in the (lo cal) population. \200 Ask about the pattern of joint symptoms over time \200 A short, striking history of marked, acute polyarticular symptoms often occurs with systemi c infection. Malaise and fever should raise suspicion of infection. Migratory arthralgia oc curs in 10% of RA patients initially: a single joint becomes in \202 amed for a few days t hen improves and a different joint becomes affected for a few days and so on. A similar pat tern can occur in post- streptococcal arthritis, occasionally in acute sarcoid, is not unus ual before frank oligoarthritis develops in Lyme disease. A history suggestive of recurrent enthesial lesions (e.g. previous tennis elbow or plantar fasciitis) or \200\230injuries \200\231, which have been \200\230slow to heal \200\231 and episodic or persist- ent in \202 ammatory back or neck pains is typical in patients with PSA. Recurrent pains from vari ous musculoskeletal lesions, which have occurred either from injury or developed insidiousl y, are typical in patients with underlying hyper- mobility. Lesions are often mild and sign s slight. Chronic pain is well recognized. There is a low incidence of ankylosing spondylitis (AS) in patients aged >65 years with bac k and joint pains. Generalized OA is rare in young men and unusual in women <40 years. With an incidence of less than 1:106 autoimmune polymyositis (PM) is rare compared with PMR whi ch has an incidence of about 1:10 000 (age >50 years). SLE is up to 5 times more common in black than in white races. Osteomalacia occurring in temperate zone \200\230western \200 \231 populations is more likely in economically deprived than in af \202 uent areas, in th e institutionalized elderly than in young adults, and in some Asian ethnic groups, rather t han Caucasians. The history of the pain at different sites \200 A good history should give you the anatomical site of pains and should be able to reveal th e tissue of origin in the majority of cases. CHAPTER 1 Clinical assessment of rheumatological disease 19 Table 1.6 Common infections associated with arthralgias and an acute phase response Table 1.7 The major myopathies Process Conditions Infection Features Infectious Viruses (e.g. in \202 uenza, Hep B/C, Cocksackie, HIV) Rheumatic fever (group A B haemolytic Strep) Acute infection 1-2/52 earlier; fever, rash, carditis. High ASOT (80%), +ve anti-DNAaseB Ig M, throat swab culture +ve. Bacteria (e.g. B burgdorferi) Other (e.g. malaria, toxoplasmosis) Endocrine or metabolic Hypo/hyperthyroidism, hypercortisolism, hyperparathyroidism Post-streptococcal Acute infection 3 \200\2234/52 earlier, tenosynovitis. Hypokalaemic, hypocalcaemic Parvovirus B19* Severe \202 u-like illness at outset, rashes. Anti-B19 IgM. Autoimmune Polymyositis, dermatosmyositis, SLE, scleroderma, Sjogren \200\231s Rubella (also post-vaccine) Fever, coryza, malaise, rash. Culture and anti-Rubella IgM. Vasculitides, myasthenia gravis, eosinophilic fasciitis Hepatitis B Fever, myalgia, malaise, urticaria, abnormal LFTs. Bilirubin and ALT elevated; anti-HbsAg/H bcAg +ve. Neoplastic Carcinomatous paraneoplastic Drug-induced Anti-lipid (statins, clo \201 brate, etc.), colchicines, *D-penicillamine, AZT, *chloroqui ne, ciclosporin, alcohol and opiates (rhabdomyolysis) B burgdorferi (Lyme) Tick bites, fever, headache, myalgia, fatigue, nerve palsies. Anti-Borrelia IgM. Muscular dystrophies Limb-girdle, fascioscapulohumeral Toxoplasma gondii Myositis, parasthesias, anti-toxo IgM. The features of parvovirus infection can be quite different in children Congenital Mitochondrial myopathy, myophosphorylase de \201 ciency, lipid storage Widespread \200\230muscle \200\231 pain (see Table 1.7) Patients who report muscle pains m ay have muscle pains, but also radicular, referred, and enthesial pains can be mistaken as arising from muscle. \200 \200 Drugs most likely to cause a painful myopathy Ischaemic pains \200 Patients may have little concept of ischaemia and might describe their symptoms in the cont ext of muscles, and in a muscular distribution. Ischaemic muscle pain often occurs predicta bly in association with repeated activity, and eases or resolves on rest. The distribution of pains may give clues as to sites of underlying pathology, e.g. upper limbs in subclavian artery stenosis or thoracic outlet syndrome or, typically, thighs, and calves in atheroscl erotic vascular disease or lumbosacral spine/lumbar nerve root stenosis. Sitting forward ma y relieve the latter. Ischaemic pains in the context of a rash may suggest systemic vasculi tis. The myalgia may be \201 bromyalgia or enthesitis. Neuromeningeal in \202 ammation in neu rosarcoid might result in perceived muscle pains. Pain locating to muscle group areas may b e ischaemic in origin (particularly neural claudication type pains in legs). The differenti al of polymyositis and dermatomyositis is wide, although many conditions are rare. Features of a history of myalgia \200 PMR (rare <55 years), myositis, and endocrine/ meta-bolic myopathies typically affect proxi mal limb and truncal musculature, but PMR is also associated with giant cell arteritis (GCA ), and therefore may present with headache, fatigue, and lassitude. Though rare, truncal mu scle pain and stiffness can be a presenting feature of Parkinson \200\231s disease. Cramp-l ike pains may be a presenting feature of any myopathy. Some patients can interpret radicula r (nerve root) pains as \200\230cramp-like \200\231 and, therefore, explain their presence in a muscular distribution. In \202 ammatory and endocrine/metabolic myopathies are not a lways painful. Some genetic muscle diseases (e.g. myophosphorylase, acid maltase de \201 c iency), can present atypically late (in adults) with progressive muscle weakness. Severe ac ute muscle pain is commonest in viral, neoplastic and drug-induced myopathies. Some toxic c auses may result in rhabdomyolysis, myoglobinaemia, and renal failure. In severe, acute myo pathy consider also the rare eosi- nophilic fasciitis or eosinophilic-myalgia syndrome (tox ic reaction to L-tryptophan). Low-grade episodic muscle pain might denote an undis- closed hereditary metabolic myopathy. Widespread pain due to bone pathology \200 Bone pains are unremitting and disturb sleep. They could denote malignancy. Major diagnoses to consider include disseminated malig- nancy, multiple myeloma, metabolic bone disease (e .g. renal osteodystrophy, hyperparathyroidism, osteomala- cia), and polyostotic Paget \200 \231s disease. Past medical history Direct questioning is often required, as previous problems may not be regarded as relevant by the patient. \200 Previous lesions that could have been due to enthesitis, previous psoriasis even if mild an d a family history of psoriasis are all relevant to making a diagnosis of PSA. Previous in \202 ammatory bowel disease, diarrhoeal or dys- enteric illness, uveitis, or urogenital in fection symptoms might be relevant to a diagnosis of SpA. For those in whom myalgia/myositi s seems likely: pre- ceding viral illness, foreign travel, previous erythema nodosum, i.e. previous sarcoid, drug, and substance use or abuse \200\223 all might be relevant. WIDESPREAD PAIN (IN ADULTS) 20 \200 For all patients: weight loss or anorexia (?malignancy); temperatures or night sweats (?vas culitis or infection); sore throat (?post-streptococcal condition); rashes (?Lyme disease, SLE, DM, PSA, vasculitis, sarcoid, SAPHO, Beh et \200\231s Disease). For those with widesp read bony pain: history of rickets (?privational osteomalacia); chronic renal disease (will precede renal osteodystrophy and may predispose to osteoarticular deposition of \2372-mic roglobulin and crystal arthritides). RA is associated with bronchiectasis. Pericardial pains and pericarditis is not unusual in SLE patients prone to get serositis. The commonest neoplasm in patients diagnosed with carc inomatous myositis, is of the lung. Chronic dry cough can be associated with interstitial l ung disease and dryness of airways (Sj gren \200\231s). The relevance of gastrointestinal symptoms and diseases \200 Patients may have overlooked volunteering abdominal and gut symptoms especially if symptoms have resolved. There are many links between bowel disease and polyar- thralgia/polyarthrit is (e.g. Crohn \200\231s Disease, UC, Sj gren \200\231s, Whipple \200\231s). Ask speci \201 cally about previous severe diarrhoeal or dys- enteric illnesses, which, if due to Cam pylobacter, Yersinia, Shigella, or Salmonella, may be relevant to diagnosing reactive arthr itis/SpA. Gut smooth muscle may be affected in PM and sclero- derma (dysmotility), and give rise to dysphagia and abdominal pain. Non-speci \201 c bowel symptoms are relatively comm on in Sj gren \200\231s (?pancreatic exocrine dysfunction), unusual in SLE, but occur (?se rosal lesions or thromboembolic lesions) Psychosocial and sexual history \200 Preceding sexual contact and genital infection is impor- tant primarily because of an assoc iation of Chlamydia trachomatis infection with reactive arthritis and enthesi- tis/SpA. Rea ctive arthritis has an association with HIV. HIV can cause acute myositis and is a risk fac tor for pyomyositis and severe PSA. There is an association of anxiety and depression with FM (p. 479). Asking speci \201 cally about genital lesions can disclose a history of recur rent ulcers in Beh et \200\231s Disease. Family history \200 There is an hereditary component to large joint, and generalized nodal OA, PSA, and the SpA s and gout. The risk of developing any autoimmune condition is higher in families of patien ts with autoimmune diseases than generally. The relevance of neurological symptoms and diseases \200 Widespread pain accompanying neurological disease is unusual, but occurs in a few scenarios . Slowly evolving cervical myelopathy often presents with widespread stiffness and discomfo rt with pain ensuing relatively late in the progression of disease. Sometimes sensory sympt oms are not volunteered. Patients with a lesion in the cord (e.g. post-traumatic syrinx) ca n also complain about a discomfort in all four limbs, which can mimic musculoskeletal stiff ness. Pain can be prominent but is not necessarily the main complaint. Sarcoidosis can affe ct the meninges and produce \202 uctu- ating sensory symptoms often characterized by diff use dysaesthesia. Symptoms are not necessarily radicular or dermatomal. Drug history \200 The following have been reported, to cause a myopathy: lithium, chloroquine*, clofibrate, s tatins, salbutamol, penicillin, colchicine, D-penicillamine*, sulphonamides, hydralazine, c iclosporin, phenytoin, cimetidine* (muscle cramps), zidovudine, carbimazole, and tamoxifen (*painful). Myositis from D-penicillamine is not dose- or cumulative dose-dependent. It can be life threatening. Drug-induced SLE, which is characterized commonly by arthralgia, achi ng and malaise, and polyarthritis, occurs with a number of drugs, including hydralazine, pr ocaina- mide, isoniazid, and minocycline. Quinidine, labetalol, captopril, phenytoin, methy ldopa, and sulphasalazine are among others that probably cause the condition. Alcohol in ex cess can cause severe toxic myopathy occasionally resulting in rhabdomyolysis. Examination In patients with widespread pain a full medical examination is always necessary . Skin and nails \200 Nails may show prominent ridges or pits in psoriatic arthropathy, splinter hemorrhages in i nfective endo- cardtis, rheumatoid vasculitis, or antiphopholipidsyn- drome (APLS), or peri ungual erythema. Skin rashes that occur in conditions characterized by widespread pain, e.g . erythema migrans in Lyme disease, erythema marginatum in rheumatic fever, UV sensitive ra sh on face/arms in SLE, violacious rash on knuckles/around eyes/base of neck in dermatomyos itis (DM), livedo reticularis in SLE/APLS, purpuric rash in vasculitis. Psoriasis is often mild and in discrete places such as the hairline, around the waist or natal cleft. Signs of anemia are a non-specific finding in many chronic systemic autoimmune diseases. Clubbing o f the digits may be present in Crohn \200\231s disease and ulcerative colitis (associated w ith SpA), hypertrophic The relevance of cardiovascular and respiratory symptoms and diseases \200 Cardiac abnormalities are features of autoimmune rheumatic and connective tissue diseases, although infrequent at initial presentation. Cardiac infection is associated with widesprea d aches and pains (e.g. rheu- matic fever/post-streptococcal myoarthralgia, infective endoc arditis). Exertional dyspnoea owing to interstitial lung disease occurs in many patients wi th autoimmune connective tissue and rheumatic diseases. Up to 40% of RA patients may have C T evidence of lung \201 brosis. In the majority of (usually sedentary) RA patients, sympt oms are often mild. Ventilatory failure and aspiration pneumonia (?postural/ nocturnal coug h) can occur as a result of a combination of truncal striated, diaphragmatic and smooth mus cle weakness in PM. CHAPTER 1 Clinical assessment of rheumatological disease 21 osteoarthropathy and bronchiectasis (associated with RA). Oedema can occur in both upper an d lower limb periph- eries in a subset of patients presenting with in \202 amma- tory poly arthritis/tenosynovitis. The condition has been termed RS3PE (remitting seronegative symmet rical syn- ovitis with pitting oedema) syndrome. This condition occurs suddenly, often in p atients between 60 and 80 years old, and is very disabling. It can be associated with hemat ological or neoplastic disease. Acneiform rashes occur in Beh et \200\231s disease, SAPHO and in sarcoid. Increased limb tone and rigidity, most evident by stiff passive movement at a joint, is con sistent with extrapy- ramidal disease. There may be resting tremor in the hand, facial impa ssivity and \200\230stiff \200\231 gait. Diagnostic testing for fatiguability in myastheni a (strictly) requires examination before and after a placebo- controlled, double blind inje ction of an anticholinesterase. In suspected cases of PM/DM examine carefully for car- dior espiratory abnormalities. Other associated features in DM include periungual erythema/telan giectasias, (see Plate 11) erythematous violacious rash and skin calcino- sis, dysphagia an d dysphonia. Because of its associations, patients with myositis should be carefully examin ed for the following signs: dry eyes/ mouth (Sj gren \200\231s, p. 254), skin thickening/t enderness or discoloration (scleroderma), skin rashes (SLE), thyroid tenderness/enlargement (endocrine myopathy). Musculoskeletal examination Note the speci \201 c cause of joint swelling, site of tendern ess, distribution of affected sites, and any intrinsic hypermobility. \200 Bony swelling at DIPJs (Heberden \200\231s nodes) and PIPJs (Bouchard \200\231s nodes) is a feature of OA , but signs can mimic PSA. Look for any dactylitis (can be acute or indo- lent) and tendern ess of phalanges distant from joint (enthesitis/dactylitis) in PSA. Periosteal new bone at sites of chronic enthesitis may be palpable and tender in PSA, but not OA. Non-bony nodules may occur in RA, polyarticular gout, multicentric reticulohistiocytosis, or hyperlipidaemi a (xanthomata). The \200\230painful joints \200\231 may be in \202 amed tendons or enthes es. Tender tendon insertions and peri-articular bone ten- derness, without any joint swelli ng, may denote enthesis in \202 ammation associated with SpA. Tendonitis may be part of ma ny autoimmune rheumatic or connective tissue diseases (e.g. thickening of the dig- ital \202 exors and swelling of the dorsal extensor tendon sheath in the hand and tenderness/swe lling of both peroneal and posterior tibial tendons in the foot. Gross swelling with painfu l restriction of small joints is unusual in SLE. Often there is little to \201 nd on exam ina- tion of joints. General joint hypermobility may account for, or contrib- ute to, joint and other soft tissue lesions. An examination screen for hypermobility (p. 442) may be hel pful. Investigations General points \200 ESR and CRP may be raised in either infection or autoim- mune connective tissue or rheumati c diseases. A slightly increased ESR is a common \201 nding in healthy elderly people. An tinuclear antibody (ANA) may occur in association with many autoimmune conditions, in other diseases and in some healthy people. It is, therefore, not diagnostic for SLE or any singl e condition; however, high-titre ANA is often signi \201 cant and, from a converse perspec tive, SLE without ANA is rare (IF on Hep2). Rheumatoid factor (RF) is not speci \201 c for RA. For example 1:6 people with infection or an in \202 ammatory condition produce detect able RFs. Low titre RF occurs increasingly with age in healthy people. RFs occur in smokers . High titre RF occurs in Sj gren \200\231s syndrome, cryoglobulinae- mia, and other syste mic vasculitides notably. Controversy exists about the existence and diagnosis of FM. It is prudent only to make a diagnosis of FM in the presence of normal ESR, CRP, FBC (CBC), urea , electro- lytes, liver function, and thyroid function tests, and if enthesitis-related dis orders (e.g. SpAs and sarcoid) can be confidently excluded. Blood calcium, phosphate, serum immunoglobulins, ACE, and protein electrophore- sis may reasonably be added to this list. Persistently elevated complement C3 and/or serum amyloid A (SAA) would call into question t he existence of FM alone without an underlying chronic in \202 ammatory condition. If widespread myalgia is more likely than joint pain \200 Establish there is muscle pathology rather than symp- toms perceived in muscles and occurri ng in other struc- tures (e.g. entheses) or referred from elsewhere (e.g. neurological or v ascular disease). The characteristic sites of tenderness in FM (p. 442) should be recognize d. However, in FM despite discom- fort muscles should be strong. Be careful about diagnosin g FM if there are tender points at entheses, which can occur in SpA or sarcoidosis. Tendern ess of plantar fascia origin and around hind feet would be relevant in this respect. The st rength testing of truncal and some limb muscles may be dif \201 cult in the presence of pa in. Patterns of muscle weakness are not disease speci \201 c. Characteristic patterns: sym metrical proximal limb and truncal in PM/DM (p. 282 and p. 290); quadriceps and forearm/ \201 nger \202 exors in inclusion body myositis; limb muscles in mitochondrial myopathy. Muscles in PMR are not intrinsically weak. Muscle wasting is not speci \201 c, but if prof ound and asso- ciated with a short history consider neoplasia. Basic tests in patients with polyarthropathy \200 Urinalysis (dipstick) can show proteinuria or haematuria \200\223 glomerular or tubular da mage are possible. ESR and CRP are often raised in autoimmune rheumatic/ connective tissue diseases, although they are non- speci \201 c and may be normal in the early stages of the se conditions. If very high (e.g. ESR > 100 mm/h) be suspi- cious of infection or malignanc y. ESR >50 mm/h is one diagnostic criterion of giant cell arteritis. There is often no acut e phase response in patients with enthesitis (even although pain and bony tenderness may be widespread). A mild normochromic normocytic anemia often accom- panies autoimmune connecti ve tissue or rheumatic diseases, infections, and malignancy. Throat swab, ASOT, anti-DNAase B antibodies (post- streptococcal condition). \200 WIDESPREAD PAIN (IN ADULTS) 22 Other simple blood tests, which should be considered given appropriate clinical evidence fo r the relevant dis- ease: random blood sugar, thyroid function tests/thyroid antibodies, li ver function tests, and prostatic speci \201 c antigen. Joint fluid aspiration and culture is mandatory for patients in whom sepsis is a possibility. Fluid should be examined by pol arized light microscopy in suspected cases of crystal-induced synovitis. Testing serum for extractable nuclear antigens (ENAs) may be useful for characterizing the type of autoimmune process. None should be considered alone to be diag- nostic or speci \201 c for any disea se, although diagnostic information is available from certain positive or negative associat ions. In most patients presenting with a short history of widespread joint pains, radiograp hs will be normal. Referral to a sexual health clinic for detailed investiga- tions if ther e \200\231s a suggestion of recent or recurrent genital infection/symptoms may help to stre ngthen the evidence for a diagnosis of reactive arthritis. likely if studied in the acute rather than the chronic phase of the illness. In the acute c ondition denervation and muscle degeneration give rise to \201 brillation poten- tials in 74% of PM and 33% of DM patients. Other features include low-amplitude short-duration moto r unit and polyphasic potentials. Electromyography is poor at discriminating on-going muscl e in \202 ammation in myositis from steroid-induced myopathy. There are characteristic MR patterns of abnormality in PM/DM. Images can be used to identify potential muscle biopsy si tes to avoid false-negative results associated with patchy muscle in \202 ammation. Muscle biopsy \200 With sizeable tissue samples from affected muscle and judicious use of a range of laborator y techniques, diag- nostic information can be provided. Differential diagnosis needs to be discussed with the pathologist whilst plan- ning the biopsy. Myositis may be patchy and bio psy may miss affected muscle. MR is sensitive in identifying areas of muscle in \202 ammat ion. In PM, inflammatory infiltrates predominate in the endomysial area around muscle \201 bres without perifas- cicular atrophy. In DM in \202 ammation is prominent in the per imysial area and around small blood vessels and there is typically perifascicular atrophy. Routine tests do not reliably distinguish PM from cases of viral myositis. Some of the glyc ogenoses will become obviously apparent from light microscopy of biopsy material. Basic laboratory tests in patients with widespread muscle pain/weakness \200 Dipstick urinalysis: to screen for haematuria or myoglobinuria. FBC (CBC) and measures of a cute-phase response. An endocrine and metabolic screen: urea, electrolytes, creatinine, thy roxine and thyroid-stimulating hormone (TSH), blood calcium, phosphate, and 25-hydroxyvitam in D, LFTs. Elevated CK occurs in most cases of PM. Creatine kinase (CK), ALT, AST, LDH are non-speci \201 c markers of muscle damage. Speci \201 c muscle iso-enzymes of CK and LDH exist and normal range of all enzymes may vary in differ- ent populations probably mainly as a function of muscle bulk (e.g. Afro-Caribbean > Caucasian). Muscle enzymes can be eleva ted after non-in \202 ammatory muscle damage, e.g. exercise/trauma. Check for ANA and, if positive, screen for ENAs. Antibodies to certain (cytoplasmic) tRNA synthetases (e.g. Jo-1) are myositis-speci \201 c. All of the above tests may reasonably be done in cases where m uscle pains might be due to \201 bromyalgia, but other pathology needs excluding. Check f or urinary myoglobin in cases where acute wide- spread muscle pain may be associated with e xcessive alcohol or ingestion of certain drugs (cocaine, ampheta- mines, ecstacy, heroin), exercise or trauma. Patients will be at risk of renal failure. PM can be the presenting fea ture of HIV disease. Consider testing HIV serology. In HIV-positive patients, infections ca using muscle disease include TB and microsporidia. Viral myositis is often clinically indis tinguishable from PM. Serology, and PCR of muscle tissue or in \202 ammatory cells may rev eal diagnostic clues. \200 Investigations for malignancy Investigations in adults with widespread muscle or bony pain should aim to rule out malignancy, particularly myeloma and semalignancies from breast, ren al, and prostate cancers. \200 Investigations may include breast US, mammography and MR, urine cytology, PSA, renal US, se rum, and urinary protein electrophoresis. Hypercalcaemia may accompany these conditions, th us check blood calcium, phosphate, and albumin. PTH should be checked in suspected cases of osteoma- lacia (raised s to calcium/vitamin D de \201 ciency) together with 25-hydroxyvit amin D levels (low or low/normal), and ALP (high/normal). Bone scintigraphy can identify si tes of neoplasia, Paget \200\231s disease, severe osteomalacia. Bone biopsy (maintained und ecalci \201 ed by placing sample in 70% alcohol) of affected sites will be diagnostic in s ome, but not all, cases of osteomalacia, osteoporosis, renal osteodystrophy, malignancy, an d Paget \200\231s disease. Good samples are hard to obtain. The best samples are obtained f rom a transiliac biopsy. Bone marrow can be aspirated for examination at the same time. Electrophysiology and imaging in patients with muscle conditions \200 Electromyographic abnormalities occur in 60 \200\22370%of patients with muscle in \202 amm ation. More information is 23 Chapter 2 Investigation of rheumatic disease Plain radiography 24 Ultrasound 26 Computed tomography 30 Magnetic resonance imaging 34 Rad ionuclide imaging 36 Autoimmune serology 38 Synovial \202 uid analysis 42 Clinical neurop hysiology 44 PLAIN RADIOGRAPHY 24 Plain radiography