Such patients are often referred to rheumatologists for evaluation. A referral may (or may not) be made with a working diagnosis in place. In the following section, we have aimed to review important aspects of the history, examina tion, and initial investigations in the initial evaluation of patients who present with non localized, multicentric pains. Initial impressions \200 Think broadly about the possible diagnoses. \200 Use what you know about the epidemiology of likely conditions. For example, a 25-year-old man with joint pains is more likely to have SpA than systemic lupus erythematosus (which occurs mostly in women age 14 \200\22350) or PMR (which is a condition of the elderly), although joint pains are characteristic of all of these diagnoses. Age, sex, and racial background What clues can be drawn from the age, sex, and racial backg round? The degree to which these factors in \202 uence the likelihood of disease varies according to the prevalence of the disease in the local population. \200 Review what you know abou t the epidemiology of the major diseases. For example: \200 there is a very low incidence of ankylosing spondylitis (AS) in patients over 65 years old with back and joint pains. generalized OA is rare in young men. \200 polymyositis is 100 times less common than poly myalgia rheumatica \200 SLE is up to \201 ve times more common in Hispanics and African Americans than in Caucasians. Previous diagnoses Presenting features may be put in context early if you have knowledge of musculoskeletal associations of diagnoses that have already been made. For example: \200 Synovitis in patients with (radiological) chondrocalcinosis. \200 Arthropathy in patient s with hyperparathyroidism and hypercalcemia (see Chapter 16). Enthesitis/synovitis in patients with Crohn \200\231s disease or ulcerative colitis (see Chapter 8). Polyarticular synovitis and myalgia in patients with lymphoma. \200 Crystal-induced or B 2 -microglobulin deposition arthritis and osteodystrophy in chronic renal disease. Taking a history First, establish whether pains arise from joints or tendons/entheses, mus- cles, bone, or are neurologic (see Table 3.5). WIDESPREAD PAIN IN ADULTS 171 Table 3.5 Broad categories of conditions that may present with widespread musculoskeletal p ain Common In \202 ammatory polyarthritis (e.g., RA \200\224see Chapter 5, SpA \200\224see Chapter 8) Generalized (nodal) OA (see Chapter 6) Fibromyalgia/chronic pain syndromes (see Chapter 18) Nonspeci \201 c myalgias and arthralgias* associated with infection (e.g., viruses) Less common Myalgias and arthralgias* due to autoimmune connective tissue disease Myalgias, increased muscle in \202 ammation (e.g., polymyositis) (see Chapter 14) Myalgias and arthralgias* associated with neoplasia (e.g., lymphoma) Skeletal metastases Polyostotic Paget \200\231s disease (see Chapter 16) Rare Metabolic bone diseases (e.g., osteomalacia, renal osteodystrophy) (see Chapter 16) Metabolic myopathies (e.g., hypokalemia) Neurological disease (Parkinson \200\231s disease) In certain situations/conditions patients may complain of both muscle and joint pains. This is easily appreciated if you \200\231ve ever had in \202 uenza! Although the patient (or referral letter) may report \200\234joint pains, \200\235 take time to establish whether the pains are truly articular. Listen carefully to the description of the pains; try to determine if the patient has a sin gle condition or a number of overlapping causes of pain. Obtain a detailed history of the pain at different sites \200 A good history should help narrow the differential diagnosis considerably. For example, a 70-year-old man referred wit h \200\234widespread joint pains mostly in his legs \200\235, could have multiple weight- bearing joint OA or lumbosacral nerve root claudication symptoms. A middle-aged woman with \200\234hand and neck pain \200\235 could have an arthropathy or radicular pain associated with cervical spondylosis. \200 Widespread pain due to bone pathology could be due to sk eletal metastasis. Bony pain is often unremitting, and changes little with changes in postu re and movement. One pitfall is to assume that all pains arise from a single pathological process. For examp le, in an older patient, shoulder pain could be caused by PMR, OA, shoulder impingement syn drome, radicular pain, or a combination of all of these. CHAPTER 3 Patterns of disease presentation 172 Joint pain at rest, after rest, or with joint use? How do you establish whether pains arise from joints or tendons/enthe- ses, and are likely to re \202 ect a single process? \200 Pain occurring with in \202 ammation is conventionally regarded as being associated with morning stiffness or stiffness after periods of rest. It tends to be prominent in condition s such as RA, SpA, PMR, and myositis. In \202 ammatory joint pain often improves during th e day. Mild degrees of immobility-associated pain and stiffness occur in some other conditions suc h as OA and \201 bromyalgia, although such forms of stiffness generally last for less tha n 1 hour. Stiffness may also be a feature of muscle spasm and soft-tissue edema. Mechanical joint damage such as OA is also painful. Unlike in \202 ammatory joint pain, mechanical joint pain is worsened by use, and improves with r est. Ask, and document in detail, which joints are affected \200 A symmetric polyarthritis aff ecting the small joints is typical for RA. RA can also present with carpal tunnel syndrome, tenosynovitis, tennis elbow, or an asymmet ric pattern of joint involvement, and can be preceded by a palindromic pattern of joint pai n (see below). Arthritis from parvovirus B19 infection may also be polyarticular and symmetric. Small joint pain in the hands occurs in nodal generalized OA. DIPs, PIPs, and thumb joints are usually affected. OA is also associated with pain in the spine, hips, and knees. The combination of sacroiliac (low back and buttock), pelvic, and lower limb joint/enthesis pain, typically in an asymmetric oligoarticular pattern, is sugge stive of SpA. Typical sites of involvement include the anterior knee, posterior heel and in ferior foot (plantar fascia). \200 Enthesitis (as the hallmark of SpA) can affect the wri sts and small joints of the hand and feet (e.g., plantar fascia origin and insertion at met atarsal heads) and may be dif \201 cult to distinguish from RA on clinical grounds alone. CPPD typically favors the large and medium-sized joints, but a picture of multiple joint in volvement similar to that in RA is possible (including tenosynovitis). Widespread arthralgias/arthritis occurs in patients with leukemia, lymphoma, myeloma, and certain infections. Ask about the pattern of joint symptoms over time \200 A short, striking history of marke d, acute polyarticular symptoms often occurs with systemic infection (see Table 3.6). Promi nent malaise and fever should raise suspicion of infection. There may be a longer history than is \201 rst volunteered. Autoimmune rheumatic and conn ective tissue diseases may evolve over a period of time and often naturally relapse and rem it; the \201 rst symptoms of disease may be dismissed by the patient as irrelevant. RA may initially present as a monoarticular or oligoarticular disease, and should be consid ered for any in \202 ammatory arthritis when an underlying disorder is not readily identi \201 ed. WIDESPREAD PAIN IN ADULTS 173 Migratory arthralgias occur in 10% of RA patients initially: a single joint becomes in \202 amed for a few days then improves and a different joint becomes affe cted for a few days and so on. A similar pattern can occur in poststreptococcal arthritis, granulomatosis with polyangiitis (Wegener \200\231s), sarcoidosis, Lyme disease, and Whippl e \200\231s disease. The onset of enthesopathy may be insidious or acute. \200 Recurrent pains from various mu sculoskeletal lesions, which have occurred from injury or have developed insidiously, are t ypical in patients with underlying hypermobility (benign joint hyper-mobility syndrome or o ther heritable diseases of connective tissue such as Ehlers \200\223Danlos, see Chapter 16) . Is there widespread muscle pain? If you think there is widespread muscle pain, remember to consider that: \200 The myalgias may be \201 bromyalgia or enthesitis. \200 Pain loca ting to muscle group areas may be ischemic or neurologic in origin, and not necessarily due to intrinsic muscle disease. The differential diagnosis of PM and dermatomyositis (DM) is broad, but many of these conditions are rare (see Table 3.7 and Chapter 14). Ask about the distribution and description of myalgias and weakness \200 True weakness ma y denote either myopathy or a neurological condition. However, patients may report a feeling of weakness if muscles are painful, there fore, rely more on your examination before deciding muscles are weak. PMR (rare in patients less than 50 years old), myositis, and endocrine/ metabolic myopathies typically present with proximal weakness. PMR does not lead to objective weakness; instead, patients experience proximal muscle pain and stiffness that is worse in the morning, and is frequently described by the patient as \200\234weakness. \200\235 Though rare, truncal muscle pain and stiffness can be a presenting feature of Parkinson \200\231s disease. Cramp-like pains may be a presenting feature of any myopathy (e.g., hypokalemic) or even motor neuron disease. However, some patients may interpret radicular ( nerve root) pains as muscle cramps. \200 In \202 ammatory and endocrine/metabolic myopat hies are often not painful. Occasionally some genetic muscle diseases (e.g., myophosphorylase, acid maltase de \201 ci ency), can present atypically late (in adults) with progressive weakness that may be mistak en for PM. Ask about the pattern of muscle pains over time \200 Severe, acute muscle pain occurs in a variety of conditions. The most common causes are viral, neoplastic, and drugs. Some toxi c causes may result in rhabdomyolysis, myoglobinuria, and renal failure. \200 Usually PM/ DM is characterized by slowly evolving but progressive proximal muscle weakness (e.g., weeks to months); pain is an uncommon feature. Low-grade episodic muscle pains may denote a previously undisclosed hereditary metabolic myopathy. CHAPTER 3 Patterns of disease presentation 174 Are the pains ischemic? \200 Lay persons may have little concept of ischemia and might de scribe their symptoms in the context of muscles and in a muscular distribution. Ischemic muscle pain often occurs predictably in association with repeated activity and eases or resolves on rest ( \200\234claudication \200\235). Consider this especially if pains are con \201 ned to a single limb or both legs. \200 The distri bution of pains may give clues as to sites of underlying pathology, e.g., upper extremities are affected by subclavian artery stenosis and thoracic outlet syndrome; lower extremities are affected by atherosclerotic vascular disease or lumb ar nerve root stenosis. Ischemic pains in the context of a highly in \202 ammatory state may suggest systemic vasculitis, such as polyarteritis nodosa. Widespread pain may be due to bone pathology \200 Bone pains are unremitting and disturb sleep. They could denote serious pathology \200\224radiographic and laboratory investigatio ns will be important. The major diagnoses to consider include disseminated malignancy, multiple myeloma, metabolic bone disease (e.g., renal osteodystrophy, hyperparathyroidism, osteomalacia) and polyostotic Paget \200\231s disease. Past medical history Speci \201 c questions are often required because previous problems m ay not be regarded as relevant by the patient. For example: \200 For those with joint pai ns a history of the following may be of help: other autoimmune diseases (increased risk of RA, SLE, etc.); Raynaud \200\231s phenomenon ( association with scleroderma, RA, and SLE); dry eyes (possible Sj gren \200\231s syndrom e); uveitis or acute \200\230red eye \200\231 (association with SpA); recurrent injuries/j oint dislocations (association with hypermobility); genital, urine, or severe gut infection (associated with SpA); psoriasis (association with SpA); diabetes (cheiroarthropathy). For those in whom myalgias/myositis seems likely: preceding viral illness (possible viral myositis); foreign travel (tropical myositis); other autoimmune dis ease (associated with PM/DM); previous erythema nodosum (sarcoid); drugs and substance abus e (see below). For all patients: weight loss or anorexia (association with malignancy); fevers or night sweats (association with infection); sore throat (possible poststreptococca l condition); persistent spinal pain (association with \201 bromyalgia); rashes (associat ion with Lyme disease, SLE, DM, vasculitis). For those with widespread bony pain: history of rickets (association with osteomalacia); chronic renal disease (will precede renal osteodystrophy and may predis pose to crystalline arthritis and osteoarticular deposition of B 2 -microglobulin). Psychosocial and sexual history \200 Preceding sexual activity and genital infection is i mportant primarily because of an association of Chlamydia trachomatis infection with reacti ve arthritis and enthesitis/SpA (see Chapter 8). Reactive arthritis has an association with HIV. HIV is also associated with polymyositis, and is a risk factor for pyomyositis. There is an association of anxiety and depression with \201 bromyalgia (see Chapter 18). WIDESPREAD PAIN IN ADULTS 175 Table 3.6 Common infections that can present with acute polyarthritis and a raised acute ph ase response Infection Common extra- articular clinical features Key laboratory diagnostic procedures in acute infection Positive throat swab culture. High ASOT (in 80%). Anti- DNAseB IgM Acute infection 1 \200\2232 weeks earlier, fever, rash, carditis Rheumatic fever (group A B -hemolytic streptococci) Post-streptococcal (?rheumatic fever) Acute infection 3 \200\2234 weeks earlier, tenosynovitis As above Parvovirus B19 (adults \200 ) Severe \202 ulike illness at onset, various rashes Anti-B19 IgM Rubella (also post- vaccine) Fever, coryza, malaise, brief rash Culture. Anti-rubella IgM Hepatitis B Fever, myalgia, malaise, urticaria, abnormal liver function Bilirubin+, ALT+, AST+, anti-HBsAg, anti-HBcAg Lyme disease (Borrelia burgdorferi) Tick bites, fever, headache, myalgias, fatigue, nerve palsies Anti-Bb IgM (ELISA + immuno \202 uorescence) Toxoplasma gondii Myositis, paresthesias Anti-Toxo IgM Even if serological tests have high sensitivity and speci \201 city, the positive predicti ve value of the test is low if the clinical likelihood of the infection is low. Therefore, do not use serological tests indiscriminately. ASOT = antistreptolysin O titer. \200 The presentation of parvovirus B19 illness may be quite different in children. Ask about travel \200 Residence in, or travel to, rural areas populated by deer might be important in indicating a risk of exposure to Borrelia burgdorferi and contracting Lyme dis ease (the spirochete is carried by ticks which colonize deer, boar, and other animals and b ite other mammals). \200 Plasmodium falciparum (intertropical areas), trypanosoma (mainly South America), trichinella, and cystercercicae infections are associated with myalgias/myo sitis. Family history Ask about family with arthritis or autoimmune diseases: \200 There is a he reditary component to large joint and generalized nodal OA and hyperuricemia/gout. The risk of developing any autoimmune condition is higher in families of patients with autoimmune diseases than generally. CHAPTER 3 Patterns of disease presentation 176 Table 3.7 The major causes of myopathies and conditions associated with diffuse myalgia (se e also Chapter 14.) Infectious myositis Viruses (e.g., in \202 uenza, hepatitis B or C, coxsackie, HIV, HTLV-I) Bacteria (e.g., Borrelia burgdorferi (Lyme)) Other (e.g., malaria toxoplasmosis) Endocrine and metabolic Hypo/hyperthyroidism, hypercortisolism, Hyperparathyroidism Hypocalcemic, hypokalemic Autoimmune diseases Polymyositis, dermatomyositis, SLE, scleroderma, Sj gren \200\231s, RA, PMR Vasculitis (e.g., PAN, Wegener \200\231s granulomatosis, rheumatoid) Myasthenia gravis Eosinophilic fasciitis Carcinomatous myopathy Idiopathic Fibromyalgia (muscles should not be weak) Inclusion body myositis Sarcoid myositis Drugs Lipid-lowering drugs (e.g., lovastatin, clo \201 brate, gem \201 brozil, niacin) Immunosuppressants (e.g., colchicine, cyclosporine, D-penicillamine*) Rhabdomyolysis (e.g., alcohol, opiates) Others (e.g., AZT chloroquine*) Muscular dystrophies Limb girdle, facioscapulohumeral Congenital myopathies \200 Mitochondrial myopathy Myophosphorylase de \201 ciency Lipid storage diseases Drugs most likely to cause painful myopathy. \200 Because of variable severity, some cond itions may not present until adulthood. Note: Guillain \200\223Barr and motor neuron dis ease may be considered in the differential diagnosis of nonpainful muscle weakness. Drug history \200 The following drugs have been reported to cause a myopathy (those marke d * are more likely to be painful): lithium, clo \201 brate, statins, penicillin, colchici ne, D-penicillamine*, sulfonamides, hydralazine, cyclosporine, phenytoin, cimetidine* (musc le cramps), zidovudine, carbimazole, and tamoxifen. WIDESPREAD PAIN IN ADULTS 177 The myositis that occurs with D-penicillamine is not dose- or cumulative dose-dependent. It can be life threatening. Drug-induced SLE, which is characterized commonly by arthralgias, aching, and malaise, and less commonly by polyarthritis, can occur with a number of drugs i ncluding hydralazine, procainamide, isoniazid, and minocycline. Quinidine, labetalol, capto pril, phenytoin, methyldopa, and sulfasalazine may also cause similar symptoms. Mild myalgias and arthralgias may be caused by a number of commonly used drugs, e.g., proton pump inhibitors, bisphosphonates and quinolone antibiotics. Alcohol in excess and some illegal drugs are associated with severe toxic myopathy occasionally resulting in rhabdomyolysis (see Table 3.7). Ask about chest pain, dyspnea, palpitations, cough, and hemoptysis \200 Cardiac abnormali ties are features of autoimmune rheumatic and connective tissue diseases, but are infrequent at initial presentation. Cardiac infection i s associated with widespread aches and pains (e.g., rheumatic fever/post-streptococcal myal gias/arthralgias, infective endocarditis). Chronic effort-related dyspnea due to interstitial lung disease occurs in many patients wit h autoimmune connective tissue and rheumatic diseases. Up to 40% of RA patients may have CT evidence of lung disease. In many sedentary patients, however, symptoms are not prominent. Dyspnea may be present at presentation. Respiratory failure and aspiration pneumonia can occur as a result of a combination of trun cal striated, diaphragmatic, and smooth muscle weakness in PM. There is an association between bronchiectasis and RA. \200 The most common neoplasm in p atients diagnosed with malignancy- associated myositis is of the lung. Ask speci \201 cally about dysphagia, abdominal pain, and diarrhea \200 Patients may not mention gastrointestinal symptoms if they have resolved. There are many links between bowel disease and polyarthralgias or polyarthri tis. Ask speci \201 cally about previous severe diarrheal or dysenteric illnesses; Campylobacte r, Yersinia, Shigella , or Salmonella , may be relevant to diagnosing reactive arthritis/Sp A. Gut smooth muscle may be affected in polymyositis and give rise to dysphagia and abdominal pain. Examination In patients with widespread pain a full medical examination is always necessary . Skin and nails (see Chapter 4) In all patients, look carefully at the skin and nails: \200 Nails may show prominent ridges or pits in psoriatic arthropathy, splinter hemorrhages in infective endocarditis, systemic vasculitis or antiphospholipid syndrome (APS), or periung ual erythema in scleroderma and the in \202 ammatory myopathies. CHAPTER 3 Patterns of disease presentation 178 Look for skin rashes in conditions characterized by widespread pain. For example: \200 erythema migrans in Lyme disease \200 erythema marginatum in rheumati c fever \200 UV sensitive rash on face/arms in SLE \200 violaceous rash on knuckles/aro und eyes/base of neck in DM \200 livedo reticularis in SLE and APS \200 purpuric rash i n vasculitis (e.g., HSP) \200 erythema nodosum in sarcoidosis. Lymphadenopathy may be present with either infection or in \202 ammation and is nonspeci \201 c. However, if prominent it may denote lymphoma. Signs of anemia are a nonspeci \201 c \201 nding in many chronic systemic autoimmune diseases. Clubbing of the digits may be present in Crohn \200\231s disease and ulcerative colitis (as sociated with SpA) and bronchiectasis (associated with RA). \200 Edema can occur in both upper and lower extremities in a subset of patients presenting with in \202 ammatory polya rthritis/tenosynovitis. The condition has been termed RS 3 PE (remitting seronegative symme tric synovitis with pitting edema). This condition is striking in that it occurs suddenly, often in patients between 60 \200\22380 years old and is very disabling. It may be associat ed with other conditions e.g., hematologic or gynecologic malignancy. Examination of the joints Important points to note when examining joints (detailed examinat ion techniques that help discriminate synovitis from other pathology at spe- ci \201 c joi nts are included in sections in Chapter 2): \200 Each joint should be compared to the joi nt on the opposite extremity, \201 rst by observation, then palpation, then by its active and passive range of motion exercises. Useful examination tools include a tape measure to record swelling (circumferential) and a goniometer (protractor with arms) to measure the range of joint mov ement. Patterns of abnormality Note the speci \201 c cause of joint swelling and site of tenderne ss, distribu- tion of affected sites, and hypermobility \200 In nodal generalized OA, ost eophytes (bony swelling \200\224may be tender) can be noted at DIPs (Heberden \200\231s nod es) and PIPs (Bouchard \200\231s nodes). Periosteal new bone at sites of chronic enthesitis may be palpable and tender. Nodules may occur in nodal OA, RA, polyarticular gout, ANCA- associated vasculitis (Churg-Strauss nodules), multicentric reticulohistiocytosis (see Plat e 16), or hyperlipidemia (xanthomata). Soft tissue swelling with tenderness and painful restriction of the joint on movement sugge sts an in \202 ammatory arthritis. There is often adjacent muscle wasting. This is most ea sily appreciated in the interosseous muscles in patients with hand arthritis, or the quadri ceps in patients with knee arthritis. WIDESPREAD PAIN IN ADULTS 179 The \200\234painful joints \200\235 may be in \202 amed tendons or entheses. Tender tendon insertions and periarticular bone tenderness, often without any joint swelling, may denote enthesis in \202 ammation associated with SpA. \200 Tendonitis may be part of man y autoimmune rheumatic or connective tissue diseases. Look speci \201 cally for thickening of the digital \202 exors and swelling of the dorsal extensor tendon sheath in the hand, and tenderness/swelling of both peroneal and posterior tibial tendons in the foot. Gross swelling with painful restriction of small joints is unusual in SLE. Often there is little to \201 nd on examination of joints. General joint hypermobility may lead to joint and other soft tissue lesions. An examination screen for hypermobility (see Chapter 16) may be helpful (see Table 3.8). Check also for a ssociated features. Examination of patients with widespread myalgias \200 Check for muscle tenderness and wea kness. Document the distribution. Is there evidence of neurologic or vascular disease? In the past, \201 bromyalgia was diagnosed based on tenderness at characteristic sites (see Figure. 3.1). However, a diagnosis of \201 bromyalgia should be considered in any patient with chronic, widespread pain. Despite discomfort, the muscle s should be strong. Examine the strength of both truncal and limb muscle groups (see Figure 3.2). In the presence of pain it may be dif \201 cult to demonstrate subtle degrees of muscle weakness. Patterns of muscle weakness are not disease speci \201 c; however, there are some characte ristic patterns: symmetric proximal extremities in polymyositis and dermatomyositis; quadri ceps and forearm/ \201 nger \202 exors in inclusion body myositis; limb muscles in mitoc hondrial myopathy. (Note: using speci \201 c apparatus physical therapists can help docume nt isometric muscle strength in certain muscle groups.) Muscles in PMR are not intrinsically weak. \200 Muscle wasting is not speci \201 c. If w asting is profound and rapid, consider neoplasia. Wasting will occur in most long-standing myopathies. \200 Check for increased limb tone and rigidity \200\224most evident by passive movement at a joint \200\224consiste nt with extrapyramidal disease. There may be resting tremor in the hand, facial impassivity , and \200\234stiff \200\235 gait. Muscular tone in the limbs may also be increased in mot or neuron disease (MND); however, if presenting with muscle pains, the patient with MND is more likely to have a lower motor neuron pattern of neuronal loss (progressive muscular atr ophy) with muscular weakness/ wasting, \202 accidity, and fasciculations. The fatigability of myasthenia gravis can be identi \201 ed by determining the length of t ime the patient can keep his arms extended in front of him, or maintain an upward gaze. Muscle pains or cramps due to large-vessel ischemia are likely to be associated with muscle s that are nontender at rest and strong. Look for diminished pulses or bruits on your exami nation, and con \201 rm your \201 ndings by imaging (e.g., ultrasound, CT angiogram, or MR). In suspected cases of polymyositis and dermatomyositis, carefully examine for cardiopulmonary abnormalities. Other associated signs CHAPTER 3 Patterns of disease presentation 180 Table 3.8 Features of the benign joint hypermobility syndrome (BJHS). See also p. 486, for new \200\234Brighton \200\235 criteria. Ability to extend \201 fth \201 nger >90 at MCPJ (score 1 + 1 for R + L) Examination screen (scored out of 9) Ability to abduct thumb (with wrist \202 exion) to touch forearm (score 1 + 1) Extension of elbows >10 (1 + 1) Extension of knees >10 (1 + 1) Ability to place hands \202 at on \202 oor when standing with knees extended (1) Associated features Prolonged arthralgias Skin striae, hyperextensibility, and abnormal scarring Recurrent joint dislocations Varicose veins Uterine/rectal prolapse Recurrent soft-tissue lesions Marfanoid habitus (arm span > height) Eye signs: drooping eyelids, myopia, down-slanting eyes Tenderness of skin overlaying trapezius Low cervical spine Midpoint of trapezius Supraspina tus Pectoralis, maximal lateral to the second costochondral junction Lateral epicondyle of the elbow Upper gluteal area Low lumbar spine Medial fat pad of the knee Fig. 3.1 Typical sites of tenderness in \201 bromyalgia. in dermatomyositis include periungual erythema/telangiectasias, erythematous violaceous ras h and skin calcinosis; include dysphonia and swallowing abnormalities in both polymyositis and dermatomyositis. Because of its associations (see Table 3.7), patients with myositis should be carefully exa mined for the following signs: dry eyes/ mouth (Sj gren \200\231s \200\224see Chapter 12 ), skin thickening/tenderness or WIDESPREAD PAIN IN ADULTS 181 discoloration (scleroderma \200\224see Chapter 13), skin rashes (SLE \200\224see Chapter 10 ), thyroid tenderness or enlargement (endocrine myopathy). Diagnostic procedures General points \200 ESR and CRP may be higher than normal in the se tting of infection, malignancy, or active rheumatic disease. A slightly elevated ESR is a c ommon \201 nding in healthy elderly people. A positive ANA may occur in association with many autoimmune conditions, in other diseases (see Table 3.9) and in some healthy people. It is, therefore, not diagnostic for SLE or any single condition; however, high-titer ANA may be signi \201 cant and conversely, ANA- neg ative SLE is rare. ACPA (such as CCP) are more speci \201 c for RA than is RF, which can be positive in a number of in \202 ammatory conditions. Controversy exists about the diagnosis of \201 bromyalgia. It is prudent only to make a d iagnosis of \201 bromyalgia only when in \202 ammatory disorders can be con \201 dently excluded. Basic tests in patients with polyarthropathy \200 Urinalysis (dipstick) may show proteinu ria or hematuria. Both glomerular and tubular damage are possible. Glomerulonephritis (in SLE, vasculitis, or endo carditis, for example) is usually associated with signi \201 cant proteinuria and hematuri a simultaneously. These patients will need urgent evaluation by a nephrologist. ESR and CRP are nonspeci \201 c and may be normal in the early stages of these conditions. If very high (e.g., ESR >100), consider infection or malignancy. There is often no evidence of an acute phase response in patients with enthesitis (even though p ain and bony tenderness may be widespread). A mild anemia and thrombocytosis may accompany in \202 ammation. Throat swab, anti-Streptolysin O titer (ASOT), and anti-DNAseB antibodies may be useful to identify a post-streptococcal condition. \200 Other simple bl ood tests that should be considered in the appropriate setting: random blood sugar (diabetes); TFTs/thyroid antibodies (hyper/hypothyroidism); pro static speci \201 c antigen (malignancy). \200 Joint \202 uid aspiration and culture i s mandatory for patients in whom sepsis is a possibility. Fluid should be examined by polar ized light microscopy in suspected cases of crystal-induced synovitis. \200 In patients w ho are ANA-positive, testing serum for extractable nuclear antigens (ENAs) may be useful for characterizing the type of autoimmune process. Ro , La, Sm, and RNP positivity are each found in a slightly different spectrum of disorders. In many patients presenting with a short history of widespread joint pains, radiographs wil l be normal. An early sign of joint in \202 ammation is periarticular osteopenia, but this is not speci \201 c for any particular disorder. Recognized types of erosions and their d istribution can be noted by experienced radiologists in speci \201 c conditions (e.g., RA, psoriatic arthritis, gout). CHAPTER 3 Patterns of disease presentation 182 (a) Functional Stand from low chair. Arms folded Sit from lying. Arms folded (b) Specific resisted (i) Patient resists downward force on abducted arms Patient lifts head and neck against a resistance on the forehead (ii) Patient resists force downwards on thigh (iii) Fig. 3.2 Screening examination for proximal myopathy. (a) Functional movements requiring tr uncal and proximal lower limb muscle strength. (b) Resisted movement testing of deltoid (i) , longitudinal \202 exors of the neck (ii), and iliopsoas/quadriceps (iii) strength.