Saturnine gout, which is associated with lead exposure (e.g., moonshine, welders), is more likely to lead to polyarticular attacks. Hypertension and hypertriglyceridemia are associated with gout. \200 A history of renal s tones (urate) may be a clue to hyperuricemia and associated gout. Attacks of gout and CPPD arthritis can be precipitated by any nonspeci \201 c illness, trauma, or surgery. The most common associated metabolic disorder is hyperparathyroidism (10% of cases). Though uncommon, hypomagnesemia, hypophosphatasia (low alkaline phosphatase activity), hemochromatosis, Wilson \200\231s disease, and ochronosis are all as sociated with CPPD arthritis. Calcium oxalate crystal arthritis can be seen as a rare compl ication of hemodialysis. Link with infection Many types of infection are linked to oligoarticular arthritis. Often a high index of suspicion is needed to make a link: \200 Speci \201 c infections are dire ctly or indirectly associated with arthritis. \200 Viruses, bacteria, protozoa, helminthe s, and fungi can all directly invade joints. The range of systemic features is wide and pat hogens can cause both polyarticular and oligoarticular patterns of joint involvement. \200 The infections recognized to trigger reactive arthritis are Salmonella, Yersinia , Shigel la , Campylobacter and Chlamydia . The development of reactive arthritis in those who acqui re chlamydial (nongonococcal) urethritis is relatively uncommon (about 1 in 30). Acute HIV infection is associated with a subacute oligoarthritis commonly involving knees and ankles. Chronic arthritis, diabetes, immunode \201 ciency, and joint prostheses are all risk factors for septic arthritis. CHAPTER 3 Patterns of disease presentation 156 Lyme disease should be considered a cause of oligoarthritis in patients with a remote histo ry of erythema chronicum migrans (i.e., macule/ papule initially, expanding 0.5 \200\2231 c m/day to a mean diameter of 15 cm (range 3 \200\22368 cm), often fading without treatment i n 3 \200\2234 weeks). \200 Migratory arthritis is typical in untreated rheumatic fever; h owever, persistent monoarthritis is a common \201 nding in treated patients. \200 A his tory of circumcorneal eye redness with pain, photophobia, and blurred vision may be due to anterior uveitis most commonly associated with SpA but als o seen with sarcoid, Beh et \200\231s, and Whipple \200\231s disease. Family and social history There may be important clues from the family and social history: \200 Both gout and SpA have a familial component. Between 6 and 18% of patients with gout also have a family history of gout. There may be a family history of SpA or uveitis in pat ients who have reactive, psoriatic, or enteropathic arthritis or AS. Gout in young adults suggests an inherited abnormality (usually increased urate production from 5-phosphoribosyl-1-pyrophosphate synthetase activity, since the other enzyme de \201 ciencies present in childhood). Excessive alcohol consumption is associated with gout. Alcohol can also contribute to lacti c acidosis that inhibits urate breakdown. \200 Consider Lyme disease if patients live, wo rk, or visit endemic areas. Outside of the United States, this includes Europe, Russia, China, and Japan. Peak incidenc e occurs during the summer. Brucellar arthritis is generally monoarticular and occurs primarily in areas where domestic ated animals are infected and poor methods of animal husbandry, feeding habits, and hygiene standards coexist. Ask about other associated features Associated extra-articular features include previous ey e, gastrointestinal, cardiac, and genitourinary symptoms: \200 Low-grade fever, malaise, and anorexia occur commonly in both septic arthritis and gout. Marked fever can occur in go ut and only occurs in about a third of patients with septic arthritis. Ask about any current or previous features which might suggest SpA: back or buttock pain (e nthesitis or sacroiliitis); swelling of a digit (dactylitis); plantar heel pain (plantar fa sciitis); red eye with irritation (anterior uveitis); urethritis, balanitis, cervicitis or acute diarrhea (reactive arthritis); psoriasis; symptoms of in \202 ammatory bowel disease . Beh et \200\231s disease (see Chapter 18) can cause an oligoarthritis. Other features include painful oral and genital ulcers and uveitis. The involvement of more than one joint does not rule out septic arthritis. In up to 20% of cases, multiple joints can become infected. Examination General \200 Always compare sides, to establish if the changes are symmetric or asymmetric. OLIGOARTICULAR PAINS IN ADULTS 157 It is important to establish from the examination whether there is true synovial swelling. A history of swelling is not always reliable and other, nonsynovial, pathology can present with single or oligoarticular joint pain. Examine the affected joints Examine the affected joints for tenderness. Check passive range of motion for evidence of locking or instability: \200 Acute processes such as crystal a rthritis, infection and post-traumatic effusion often lead to painful swelling, marked tend erness of swollen soft-tissues, and painfully restricted active and passive movement of the joint. These features are usually less overt with chronic arthritis. \200 Instability of an acutely in \202 amed joint or tests for cartilage damage in the knee may be dif \201 cult to demonstrate. Further examination will be necessary after drainage of joint \202 u id. Detection of enthesis tenderness around the affected joints or at other sites is a useful clue to the diagnosis of SpA. Examine other musculoskeletal structures \200 Examine the low back and typical sites of b ony tenderness \200\224sacroiliitis and enthesitis are common features of SpA. Tendonitis is not speci \201 c and can occur in gout, CPPD arthritis, SpA, and gonococcal infection. Look for skin rashes and any in \202 ammation Oligoarthritis may be part of a systemic in \202 ammatory or infectious condition. \200 Fever and tachycardia can occur with some no ninfectious causes of acute arthritis (e.g., crystal arthritis), but their presence in the context of oligoarticu lar joint swelling requires exclusion of joint infection. Gouty tophi may be seen in the pinnae and in other peripheral locations. They can be dif \201 cult to discriminate clinically from rheumatoid nodules. Polarized light microscopy 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 are common; however, crops or large painful tongue and buccal lesions associat ed with oligoarticular arthritis suggest Beh et \200\231s disease. A typical site for the osteitis (tender swelling of bone) of SAPHO syndrome is around the sternum and clavicles. Skin erythema over a joint suggests crystal arthritis or infection. \200 Associated skin rashes may include erythema nodosum (associated with ankle/knee synovitis in acute sarcoid) , purpuric pustular rashes (Beh et \200\231s, gonococcal infection, and SAPHO syndrome), erythema marginatum (rheumatic fever), or keratoderma blennhorragica (aggressive-looking r ash of the sole of the foot in Reiter \200\231s disease). Psoriasis may be associated with both synovitis and enthesitis. CHAPTER 3 Patterns of disease presentation 158 Diagnostic procedures The presence of synovitis can be con \201 rmed by obtaining US or MR of the joints in question. At larger joints, both are sensitive for the detection of effus ion and synovial thickening. In \202 ammation at periarticular or capsular entheses can al so be seen. Joint aspiration The most important investigation of a patient with monoarticular synovitis is joint aspiration and prompt examination of \202 uid. Fluid should be sent in sterile bottles for microscopy and culture: \200 The appearance of synovial \202 uid is not spe ci \201 c; however, blood or bloodstaining suggests hemarthrosis from trauma (including the aspiration attempt), a he morrhagic diathesis, hemangioma, PVNS, and synovioma. Turbidity (i.e., decreased clarity) of \202 uid relates to cellular, crystal, lipid, and \201 brinous content. Synovial \202 uid in septic arthritis and acute crystal arthritis is frequently turbid due to the high number of neutrophils. Cell counts give some diagnostic guidance but are nonspeci \201 c (see Table 3.2). There is a high probability of infection or gout if the PMN differential is >90 %. Joint \202 uid eosinophilia is not speci \201 c. \200 Polarized light microscopy of \202 uid can discriminate urate (3 \200\22320 m in length, needle-shaped and negatively bi refringent \200\224initially blue, and then yellow as the red plate compensator is rotated through 90 ) and calcium-containing crystals such as calcium pyrophosphate (positively bir efringent crystals, typically small and rectangular or rhomboid in shape). Lipid and cholesterol crystals are not uncommon in joint \202 uid samples, but their signi \201 cance is unknown. Crystals appearing in synovium less commonly but in typical settings include hydroxyapatite associated with Milwaukee shoulder (and knee) syndrome (which can be visualized by stainin g with alizarian red S), calcium oxalate in end-stage renal failure on dialysis (may need s canning electron microscopy to con \201 rm), cystine in cystinosis, and xanthine in xantho sis. The presence of crystals in joint \202 uid does not exclude infection. \200 The most co mmon causes of nongonococcal septic arthritis in Europe and North America are Staphylococcu s aureus (40 \200\22350%), Staphylococcus epidermidis (10 \200\22315%), S treptococcal spec ies (20%), and Gram-negative bacteria (15%). Radiographs Radiographs can con \201 rm an effusion, show characteristic patterns of chon- dral and bone destruction (e.g., in infection or erosive gout) and can reveal intra-articu lar calci \201 cation associated with CPPD or hydroxyapatite arthritis: \200 Septic arth ritis causes patchy osteopenia and loss of bone cortex. \200 \200\234Punched-out \200 \235 erosions (within joints or around metaphyses), soft tissue swellings (tophi), and patc hy calci \201 cation are hallmarks of chronic gout. OLIGOARTICULAR PAINS IN ADULTS 159 Intra-articular calci \201 cation may be associated with either chondrocalcinosis ( \201 ne linear or punctate \201 brocartilage calci \201 cation) or larger loose bodies (often with proli \201 c osteophytes) \200\224both are associated with CPPD arthritis. Numerous regularly shaped calci \201 c masses in a joint may be due to synovial chondromatosis (most common in middle-aged men; 50% of cases affect the knee). The presence of erosions does not implicate RA. The arthritis may be due to an enthesitis associated with SpA. Further imaging Further imaging should be discussed with your radiologists: \200 MR con \201 rmation of traumatized structures such as meniscus damage in the knee and labral damag e in the shoulder should be sought if suspected. MR can con \201 rm synovitis, although appearances are usually nonspeci \201 c. MR can al so identify enthesitis and PVNS. Laboratory tests to consider \200 CBC, acute phase response (ESR, CRP). Neutrophilia is n ot speci \201 c for infection and can occur in crystal arthritis. Blood urea, electrolytes, creatinine, and urate (e.g., hyperuricemia and renal impairment associated with gout). Blood calcium, phosphate, albumin, alkaline phosphatase ( iPTH), thyroid function tests and ferritin to screen for hyperparathyroidism, thyroid disease, and hemochromatosis, all of which can be associated with CPPD arthritis. Autoantibodies: rheumatoid factor and ACPA, such as cyclic citrullinated peptide (CCP) may help identify early rheumatoid arthritis. IgM Borellia burgdorferi serology may help diagnose Lyme disease in patients at risk (e.g., acute arthropathy or migratory arthritis). Table 3.2 Characteristics of joint \202 uid Characteristic Normal Group I (nonin- \202 ammatory) Group II (in \202 am- matory) Group III (septic) Viscosity Very high High Low Variable Color None Straw Straw or opalescent Variable with organisms Clarity Clear Clear Translucent or opaque Opaque Leukocytes (cells/mm 3 ) PMNs (%) 200 200 \200\2232000 2000 \200\22350000 >50000 <25 25 Often >50 >75 CHAPTER 3 Patterns of disease presentation 160 Antibodies to the streptococcal antigens streptolysin O (ASOT) DNAse B, hyaluronidase, and streptozyme may be useful in patients who have had sore throat, migratory arthritis, or features of rheumatic fever. Synovial biopsy \200 If there is a hemarthrosis or suspicion of PNS, MR of the joint is w ise before undertaking a biopsy to characterize the vascularity of a lesion. Consider a biopsy to evaluate a monoarthritis of unclear etiology. Biopsy may be helpful to diagnose sarcoid arthropathy, infectious arthritis, or crystalline arthropathy when the us ual diagnostic procedures are negative. Formalin \201 xation of samples is suf \201 cient in most cases. Samples for polarized l ight microscopy are best \201 xed in alcohol (urate is dissolved by formalin). Snap freez ing in nitrogen is essential if immunohistochemistry is required. Arthroscopic biopsy will yield more tissue than needle biopsy, and will allow joint irrigation. Congo red staining of synovium, ideally with polarized light microscopy, should be requested if AA, AL, or B 2 -microglobulin amyloid is a possibility. This should be considered in patients with myeloma (AL) and long-term dialysis patients ( B 2 -microglobulin). AA amyloid is an uncommon but recognized complication of rheumatoid art hritis, ankylosing spondylitis, familial Mediterranean fever, and Crohn \200\231s disease. This page intentionally left blank CHAPTER 3 Patterns of disease presentation 162 Oligoarticular pains in children and adolescents Background Disease classi \201 cation In 2001, a working group under the auspices of the International League of Associations for Rh eumatology (ILAR) met to establish a consensus regarding classi \201 cation criteria for p ediatric and adolescent arthritides (see below). For a review of these new and old autoimmu ne arthritis classi \201 ca- tions, see below and Table 3.4, and under the relevant diagno stic headings in Chapter 9. Important issues pertinent to children and adolescents \200 Compared to adults, it may be quite dif \201 cult to establish whether there is synovitis in a child \200\231s joint (see Table 3.3). An awareness of injuries and mechanical conditions that affect speci \201 c joints, notabl y at epiphyseal or apophyseal growth plates, is essential. \200 In very young children, a history from both the child and the main care provider is important. It is important to note that monoarticular or oligoarticular synovitis: may present with limb pain \200 may not necessarily present with joint pain and stiffness \200 may result in nonuse, altered use, or irritability, any of which may be the main or only complaint. Systemic juvenile idiopathic arthritis (JIA) (previously systemic onset juvenile rheumatoid arthritis (JRA)) is de \201 ned as arthritis preceded by (or occurring with) daily recurr ing fever of more than 2 weeks \200\231 duration (documented for greater than 3 days) plus one or more of the following: an evanescent, non \201 xed, erythematous rash; generalized lymphadenopathy; enlarged liver or spleen; or serositis. Persistent oligoarthritis is de \201 ned by the involvement of no more than four joints throughout the disease course. Extended oligoarthritis affects a cumulativ e total of \201 ve joints or more after the \201 rst 6 months of disease. Excluded from each group are those with: a family history of psoriasis ( \201 rst- or second degree rel ative); a positive RF; HLA B27 (males >8 years old); or systemic arthritis. Under the new system, enthesitis has a key-classifying role in the group of conditions prev iously classi \201 ed as spondyloarthropathy (SpA), now called enthesitis-related arthriti s (ERA). The de \201 nition of psoriatic arthritis has been broadened under the new ILAR classi \201 cation (see Table 3.4). The classi \201 cation criteria require arthritis beginning b efore 16 years of age and either typical psoriasis or at least three of the following: dact ylitis, nail pitting, psoriasis-like rash, family history of psoriasis ( \201 rst- and sec ond-degree relatives). Enthesitis, iritis, and HLA B27 are absent from this classi \201 ca tion. OLIGOARTICULAR PAINS IN CHILDREN AND ADOLESCENTS 163 Table 3.3 The major causes of monoarticular/oligoarticular joint synovitis or swelling in c hildren Condition Distinguishing features Septic arthritis Systemically unwell child. With TB \200\224pulmonary disease, lower limb, insidious onset, and rapid joint destruction Trauma Direct blow/forced hyperextension, hemorrhage into joint Foreign body synovitis History of injury PVNS Recurrent joint hemarthrosis Thalassemia Episodic and migratory arthritis Malignancy Acute monoarticular joint swelling, associated with leukemia and neuroblastoma Viral arthritis Associated with rash or immunization Lyme disease Exposure in endemic area, rash, positive serology Post-streptococcal Sore throat, migratory arthritis, signs of rheumatic fever FMF Ethnic grouping and familial aggregation, acute febrile episode with chest/abdominal pain Beh et \200\231s disease Rare. Orogenital ulceration and skin rashes Oligoarticular JIA Monoarticular in 60% of cases and involves two joints in 31% of cases. Diagnosis of exclusi on, associated with asymptomatic uveitis Enthesitis-related arthritis Usually age 8 or over, boys > girls, iritis, most have enthesitis, HLA B27. Sacroiliac join t involvement, low back stiffness Psoriatic arthritis* Rash, nail pitting, or other changes Sarcoid Usually associated with rash and ocular symptoms Vasculitis Rash, high ESR/CRP SLE UV-sensitive skin rash, ANA In the ILAR classi \201 cations, psoriatic arthritis is distinguished from enthesitis-rela ted arthritis (see below). Taking a history Epidemiology Recall epidemiological features associated with different gro ups and ages: \200 The peak incidence of oligoarticular JIA (or pauciarticular JRA) is between the ages of 1 and 3. It is relatively very rare after 12 years of age. Enthesitis-related arthritis (ERA or SpA) is more common in boys (ratio up to 10:1) and typically occurs after the age of 8. CHAPTER 3 Patterns of disease presentation 164 Table 3.4 ILAR classi \201 cation of arthritis in childhood (juvenile idiopathic arthritis ) ILAR classi \201 cation of juvenile idiopathic arthritis (JIA) Previous classi \201 cation Systemic arthritis* Systemic onset JRA Oligoarthritis* which is either: persistent (always 4 joints or less) extended (after 6 mon ths >4 four joints affected) Oligoarticular JRA Pauciarticular JRA Polyarthritis (RF+)* 5 or more joints affected Polyarticular JRA Polyarticular JRA (RF+) Polyarthritis (RF \200\223) Polyarticular JRA (RF \200\223) Psoriatic arthritis* Psoriatic arthritis Enthesitis-related arthritis (ERA)* SpA JCA = juvenile chronic arthritis; JRA = juvenile rheumatoid arthritis; RF = rheumatoid fact or. * See text for notes. Trauma Monoarticular synovitis may be associated with trauma: \200 Time to onset of joint swelling after trauma (<2 h) and intensity of pain (severe) may help discriminate whether a hemarthrosis is present. Intra-articular frac ture should then be suspected. An absence of a history of trauma does not rule out the possibility of osteochondritis diss ecans (only 10% are associated with trauma). \200 Be aware that nonaccidental trauma can present with traumatic joint swelling. Infection/malignancy Infection and malignancy must be ruled out in all cases of atraumatic monoarthritis: \200 An insidious onset does not rule out infection. This pattern is well recognized in TB. Joint destruction, however, may not be insidious. \200 The most common neoplastic causes of monoarticular joint swelling in children are leukemia and neuroblastoma. Rare causes of symptoms The rarer causes of monoarticular synovitis, joint swelling, or pai n, and joint-speci \201 c causes of pain in a single joint should not be forgotten: \200 Intra-articular hemangiomas, osteoid osteomas, synovial chondromatosis, and lipomatosis arborescens can occur in most joints. \200 Anterior knee pain (common in growing adolescents, especially girls). \200 Isolated hip pain conditions such as Perthes \200\231 disease. \200 Oligoarticular JIA (Pauci-JRA) of the hip is very rare. \200 Osteochondritides/avulsion fractures, e.g., Osgood \200\223Schlatter \200\231 s. \200 Osteonecrosis at typical sites, e.g., tarsal navicular, carpal lunate. OLIGOARTICULAR PAINS IN CHILDREN AND ADOLESCENTS 165 Preceding symptoms Ask about preceding symptoms of infection and rashes. Consider viral, st reptococcal, and enteric infections, and Lyme disease: \200 Oligoarthritis (or monoarthri tis) may be a reaction to an infection and may be short-lived usually lasting 3 \200\2236 w eeks, but occasionally up to 8 weeks. A streptococcal sore throat can lead on to a migratory arthritis. The differential diagnosi s would include rheumatic fever and Lyme disease. The most distinctive features of acute rheumatic fever should be sought in patients with oligoarthritis, especially if it has been partially treated with as pirin or NSAIDs, which can mask its migratory nature; these include: carditis with prolonge d PR interval, chorea, skin nodules, erythema marginatum. Salmonella, Shigella, Yersinia , and Campylobacter enteric infections are associated with reactive arthritis. Escherichia coli and Clostridium dif \201 cile infections have the potential for triggering reactive arthritis. A facial rash occurs in rubella \200\224coalescing erythema that clears as the limbs become affected; in most patients, however, a facial rash should make you think about parvovirus B19 infection (erythema infectiosum \200\224 \200\230slapped cheek \200\231 syndrome). Pink or faintly red erythema on the trunk or limbs but not the face is typical of the erythema marginatum of rheumatic fever. The outer rash margin is often disti nct and continuous. Firm, nontender skin nodules, which may have regressed, may also sugges t rheumatic fever. \200 Lyme disease causes erythema chronicum migrans, a spreading erythema from a tick bite. Because of heightened awareness, patients may present early, bef ore the classic targetoid rash has a chance to evolve. Live attenuated rubella vaccines are associated, in up to 15% people, with subsequent arthr algias and myalgias. Arthritis may occur 2 weeks after the injection and clears in a week, but symptoms can remain for a year or so. Family history Ask about a history of illness in the family or a family history of enthesit is- related (SpA) features: \200 In children suspected of having septic arthritis due to TB, establishing a history of contact with sources may be important. Due to a link with HLA B27, there may be a history of similar musculoskeletal features in family members. Examination General principles of pediatric musculoskeletal examination \200 Ensure that the child is comfortable in the environment and with the people present at the time of examination. Reassure the child that the examination will not persist if it is painful. \200 Observe s mall children playing at \201 rst. \200 Try to leave the painful area until last. CHAPTER 3 Patterns of disease presentation 166 Con \201 rmation of synovitis/enthesitis in a joint Review the features that help to con \201 rm synovitis/enthesitis in a joint: \200 It is important to establish from the exami nation whether there is true synovial swelling. Remember, a history of swelling is not always reliable and other, n onsynovial, pathology can present with single or oligoarticular joint pain (e.g., enthesiti s). Always compare both sides. Even subtle differences in range of motion may be important and denote synovial thickening. Doubt about synovial swelling can be addressed by obtaining US. Additional musculoskeletal examination Additional musculoskeletal examination must include a search for muscle atrophy , tenosynovitis, enthesitis, and spinal limitation: \200 Adjacent muscle wasting may be a clue to the severity or chronicity of joint in \202 ammation. Tenosynovitis is unusual in oligoarticular JIA, but can occur in sarcoid, occasionally in ERA/SpA, and in the polyarticular conditions. Enthesitis should discriminate between oligoarticular JIA and ERA/SpA. Commonly involved si tes include Achilles, patellar tendon, and plantar fascia insertions. Clinical detection of spinal disease in patients who develop AS or ERA/SpA is not always possible at the time of presentation of the \201 rst musculoskeleta l manifestations of the disease, i.e., enthesitis, although spinal examination assessing lo calized pain and impaired mobility should be done. Look for skin rashes and any in \202 ammation Oligoarthritis may be part of a systemic in \202 ammatory/infective condition. Look closely for skin rashes: \200 Skin erythema over lying a joint suggests infection. \200 Associated skin rashes may include erythema nodosu m, the purpuric pustular rashes of Henoch \200\223Sch nlein purpura (HSP) (extensive low er limb) or Beh et \200\231s (less \202 orid than HSP), gonococcal infection (single p ustules), SAPHO syndrome, erythema marginatum (rheumatic fever) and psoriasis. Diagnostic procedures Although synovitis may be obvious clinically, its presence in any joi nt needs to be con \201 rmed if there is doubt: \200 The soft tissue appearances of join t radiographs are suf \201 cient in con \201 rming effusion and synovial thickening in ma ny instances. US and MR can identify effusion and synovial thickening. Joint aspiration The most important investigation of a child with monoarticular synovitis i s joint aspiration and prompt examination of \202 uid. Fluid should be sent in sterile bo ttles for microscopy and culture. This procedure may be psycho- logically traumatic. Consid er using sedation (at least) in older children and a light general anesthetic in younger on es. OLIGOARTICULAR PAINS IN CHILDREN AND ADOLESCENTS 167 Synovial \202 uid appearances are not speci \201 c. However, the following guidelines may be helpful: Blood or bloodstaining suggests hemarthrosis from: trauma (including the aspiration), hemorrhagic diathesis, PVNS, synovioma, or hemangioma. Turbidity (decreased clarity) of \202 uid relates to cellular, crystal, lipid, and \201 brinous content; the joint \202 uid of septic arthritis and acute crystal arth ritis is turbid due to the high number of neutrophils present. Crystals in synovial \202 uid in children are rare. \200 The most common causes of nong onococcal septic arthritis in Europe and North America are Staphylococcus aureus (40 \200 \22350%), Staphylococcus epidermidis (10 \200\22315%), streptococcal species (20%), and Gra m-negative bacteria (15%). Gonococcal infection should be considered a possibility in teena gers. Radiographs Radiographs can con \201 rm an effusion and show characteristic pat- terns of chondral epiphyseal and bone destruction (e.g., in infection or malignancy): \200 In sept ic arthritis, osteopenia and loss of bone cortex are classic signs (although their absence does not rule out septic arthritis). The main differential diagnosis is malignancy. If calci \201 ed, loose bodies due to osteochondritis dissecans may be visible. Erosions can occur in oligoarticular JIA or in ERA/SpA (entheseal). \200 Discriminating e rosions from ossifying cartilaginous epiphyses in normal joints (which can appear irregular ) is sometimes dif \201 cult. Bilateral views are sometimes helpful in this respect. Joint space narrowing is dif \201 cult to con \201 rm from radiographs because of normal changes in epiphyseal cartilage thickness, operator error, and dif \201 culty in weight be aring on painful joints. Joint destruction is a characteristic of polyarticular JIA. Further imaging Further imaging should be discussed with your radiologist. US and scintig- raphy can con \201 rm synoviti s and its pattern of joint involvement. CT and MR are useful in discriminating against the causes of synovitis: \200 US is a very sensitive investigation for detection of synovitis and is particularly useful in evaluating the hip. US and MR can detect erosions earlier than radiographs. \200 When malignancy and infectio n are suspected, bone scan may help identify or rule out additional lesions. Because of its high sensitivity, bone scan can be useful in establishing whether signi \201 cant bone/joint pathology is present in children with joint symptoms but few clinical \201 ndings. In a normal joint, MR differentiates all the major joint structures including epiphyses. Se dation may be needed in young children. MR is an accurate and sensitive tool for identifying joint and epiphyseal damage at an earl y stage of a disease process. This may be invaluable for example if there is any doubt abou t the status of oligoarticular JIA CHAPTER 3 Patterns of disease presentation 168 or peripheral joint involvement in ERA/SpA, since early treatment can prevent permanent def ormities and disability. Laboratory tests Laboratory tests should provide or exclude evidence of infection, give dis - criminatory diagnostic information, and exclude nonrheumatic diseases: \200 A predomina nce of bands on CBC implies infection. Neutrophil predominance may be seen with a variety of in \202 ammatory states, and is less speci \201 c for infection. Interestingly, monoarticular JIA can be associated with normal indice s. A low platelet or white cell count but elevated acute phase indices may be suggestive of an underlying malignancy. Antibodies to streptolysin O (ASOT) may be helpful in patients who have had sore throat, mi gratory arthritis, or features of rheumatic fever. If there is persistent clinical suspicio n despite a normal ASOT, antibodies to streptococcal DNAase B, hyaluronidase, and streptozy me may be of value. Autoantibodies: a single positive test for RF has little value. Repeatedly positive tests m ight suggest (RF+) JIA. ANAs are present in 40 \200\22375% of children with oligoarticular JIA (JCA). They are not disease-speci \201 c, but identify a subset within it at particula r risk of (often asymptomatic) uveitis. Lyme serology may be helpful in a patient with an acute arthropathy or migratory arthritis. Synovial biopsy \200 If there is a hemarthrosis or suspicion of PVNS, MR of the joint is wise before undertaking biopsy to characterize the vascularity of a lesion. \200 Biopsy m ay be helpful to evaluate a persistent monoarthritis of unclear etiology; biopsy may help d iagnose sarcoid arthropathy, malignancy, and chronic infectious arthritis due to atypical p athogens. Arthroscopic biopsy will yield more tissue than a needle biopsy. Direct viewing may add diagnostic information and allow joint irrigation. This page intentionally left blank CHAPTER 3 Patterns of disease presentation 170 Widespread pain in adults Widespread (musculoskeletal) pain is a common reason for adults t o seek medical advice (see Table 3.5). Although some of these patients will have a polyarti cular arthritis, many conditions are characterized by musculoskel- etal symptoms, some of w hich may be diffuse or multicentric. In addition, the interpretation and reporting of sympt oms varies considerably and can be a source of confusion. 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