Showing posts with label Joint pain. Show all posts
Showing posts with label Joint pain. Show all posts

Sunday, May 3, 2015

Joint Pain a Major Issue in Chronic HCV Infection

Joint Pain a Major Issue in Chronic HCV Infection
by Diana Swift
Contributing Writer


Smoking increases risk of arthralgias in hepatitis C.

Patient-reported joint pain is prevalent in those with chronic monoinfection with hepatitis C virus (HCV) or monoinfection with immunodeficiency virus (HIV), as well as in patients with HIV/HCV coinfection, according to a study published online in BMC Musculoskeletal Disorders on April 19, 2015. But chronic HCV patients report more arthralgia.

The study, led by Alexis R. Ogdie, MD, a rheumatologist at the University of Pennsylvania in Philadelphia, found that chronically HCV-monoinfected patients more frequently reported arthralgias compared with HIV/HCV-coinfected or HIV-monoinfected persons.

Joint pain was more commonly reported in HCV-monoinfected than HIV/HCV-coinfected (71% versus 56%; P=0.038) and HIV-monoinfected patients (71% versus 50%; P=0.035).

"These results suggest that joint pain remains a major health concern and a determinant of health-related quality of life among these patients," wrote Ogdie and her associates, adding that healthcare providers should address modifiable risk factors for joint pain such as smoking.

HCV is the most common blood-borne infection in the U.S., infecting 4 million persons and having a range of extrahepatic manifestations, including renal, dermatological, neurological, and rheumatological. "While chronic HCV-induced inflammation is generally thought to be a key contributor to these manifestations, the mechanisms by which they occur remain unclear," the researchers wrote.

The cross-sectional study enrolled 202 patients (173 males) and conducted standardized interviews in 79 HIV/HCV-coinfected, 93 HCV-monoinfected, and 30 HIV-monoinfected patients in hepatology and infectious-disease clinics at three U.S. centers. Age and gender distributions were similar across all three groups, while, racially, more than half of participants were black. The Multi-Dimensional Health Assessment Questionnaire (MD-HAQ) evaluated joint pain and associated symptoms, and interviewers collected information on potential risk factors.

Logistic regression determined adjusted odds ratios (aORs) with 95% confidence intervals (CIs) of joint pain associated with risk factors among chronic HCV-infected and HIV-infected patients. Joint pain was reported by more HCV-monoinfected than HIV/HCV-coinfected patients: 71% versus 56% (P=0.038) and by more HIV-monoinfected patients: 71% versus 50% (P=0.035).

In all groups, the fingers, knees, and back were the most frequently cited areas of joint pain. The distribution of painful joints was similar among the groups, although HCV-monoinfected patients more commonly reported finger pain compared with coinfected patients (41% versus 27%, P=0.035) and HIV-monoinfected patients (41% versus 23%, P=0.067).

A previous diagnosis of arthritis and current smoking were risk factors for arthralgias in both infections. In chronic HCV-infected patients, arthritis had an aOR of 4.25 (95% CI 1.84-9.81), and smoking an aOR of 5.02 (95% CI 2.15-11.74). In HIV-infected patients the aOR for arthritis was 5.36 (95% CI 2.01-14.25) and for current smoking 6.07 (95% CI 2.30-16.00).

Smoking has been associated with musculoskeletal pain and the development of, and worse disease activity in rheumatoid arthritis. This is the first study to report on its link to joint pain in chronic HCV. The authors cited the need for further research to determine whether smoking cessation improves arthralgia in chronic HCV patients.

While the etiology of joint pain in chronic HCV remains unclear, the authors noted that immune activation, direct deposition of viral particles in the synovium, and the high prevalence of concomitant mood disorders might be important contributors to the arthralgias commonly reported by chronic HCV-infected patients. More than half of patients reporting joint pain also self-reported depression and anxiety on the MD-HAQ.

The differences in joint pain prevalence among the three groups raise important questions for further study, the authors wrote. "Hypothesized explanations for these findings include differences in unmeasured environmental exposures among the groups or potentially a decrease in local inflammation related to immune dysfunction in HIV infection, resulting in a decreased effect of chronic HCV in the HIV/HCV-coinfected patients." Additionally, HIV-infected patients may be more tolerant of joint discomfort because of the higher priority placed on more serious complications of their disease. With HCV patients reporting a high prevalence of depression, anxiety, and sleep disturbance, depression and anxiety could have contributed to a higher prevalence of joint pain since mood and arthralgia are strongly linked.

Addressing study limitations, the authors noted the cross-sectional design, use of convenience sampling, the inability to perform physical examinations and imaging studies to rule out osteoarthritis, the relatively small sample, and the biasing possibility that patients with joint pain may have been more likely to complete the survey. Additionally, the study was unable to determine the specific etiologies for joint pain. Furthermore, some patients were prescribed analgesic medications and have self-reported joint pain less frequently. Also, because the study evaluated joint pain present within the week before the interview date, some patients with intermittent joint pain may not have been identified in this study.

"Future studies should determine the etiologies and strategies for management of joint pain, including fibromyalgia, in patients with chronic HCV and HIV infection, as well as the mechanisms for modulation of joint symptoms in HIV/HCV-coinfected patients," the authors concluded.

This study was funded by the American College of Rheumatology Research Foundation. The lead author was supported by the American College of Rheumatology Research and the National Institute of Arthritis and Musculoskeletal and Skin Diseases, and another author by the National Institute of Allergy and Infectious Diseases.

The authors declared no competing interests.
Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

Last updated 05.03.2015

Wednesday, March 16, 2011

The Approach to the Painful Joint

The Approach to the Painful Joint

Author: Alan Baer, MD, Associate Professor of Medicine, Department of Medicine, Johns Hopkins University; Clinical Director, Johns Hopkins Rheumatology Practice at Good Samaritan Hospital; Chief of Rheumatology, Good Samaritan HospitalCoauthor(s): Vinod Patel, MD, Medical Director, Jefferson Family Medicine Center; Clinical Assistant Professor, Department of Family Medicine, State University of New York at Buffalo; Robert McCormack, MD, Associate Professor of Clinical Emergency Medicine, University at Buffalo School of Medicine and Biomedical Sciences

Contributor Information and Disclosures



Joint pain can be caused by diverse processes, including inflammation, cartilage degeneration, crystal deposition, infection, and trauma. The differential diagnoses of joint pain are generated in large part from the history and physical examination.1 Screening laboratory test results serve primarily to confirm clinical impressions and can be misleading if used indiscriminately. The initial aim of the evaluation is to localize the source of the joint symptoms and to determine the type of pathophysiologic process responsible for their presence.


Joint pain may arise from structures within or adjacent to the joint or may be referred from more distant sites. Sources of pain within the joint include the joint capsule, periosteum, ligaments, subchondral bone, and synovium, but not the articular cartilage, which lacks nerve endings. Determination of the anatomic part responsible for joint pain is often a difficult yet critical task, since it guides the approach to diagnosis and therapy. Knowledge of the anatomy of complex joints, such as the knee, shoulder, and ankle, aids in this assessment.

The evaluation of joint pain, both in terms of the history and the physical examination findings, is best achieved through an understanding of the basic pathophysiologic types of joint disease. These include synovitis, enthesopathy, crystal deposition, infection, and structural or mechanical derangements. These types of joint disease are not mutually exclusive. Examples of pathologic processes that commonly coexist include crystal deposition in osteoarthritis, synovitis in enthesopathies, and cartilage destruction in chronic synovitis.


The synovial membrane is the principal site of inflammation in persons with rheumatoid arthritis (RA) and many other inflammatory arthritides.2 Synovitis is characterized pathologically by neovascularization; infiltration of the synovium with lymphocytes, plasma cells, and macrophages; and synovial lining cell hyperplasia. These cause synovial proliferation, recognized clinically by warmth, tenderness, and a boggy consistency of the soft tissues overlying the involved joint. The inflamed synovium may infiltrate and erode intra-articular bone and cartilage.


The enthesis is the transitional zone where collagenous structures such as tendons and ligaments are interwoven into bone.3 Other examples of entheses include the interface between cortical bone and the periosteum and between vertebral bodies and the annulus fibrosus. It is the principal site of pathology in the seronegative spondyloarthropathies. As a result of inflammation at these interfaces, the radially oriented collagen fibers undergo metaplasia, forming fibrous bone. These metaplastic transformations result in new bone formation (periostitis), gradual ossification of syndesmoses (eg, the sacroiliac joints), and syndesmophyte formation along the outer fibers of the vertebral discs. When enthesitis occurs in a diarthrodial joint, a secondary synovitis may develop.

Crystal deposition

The deposition of crystals in articular structures may lead to symptomatic joint disease. The responsible crystals include monosodium urate, calcium pyrophosphate dihydrate, basic calcium phosphate (including hydroxyapatite), and calcium oxalate.

Monosodium urate crystal deposition occurs on the surface of hyaline cartilage, within the synovium and in periarticular structures, including tendon sheaths and bursae. As a result, inflammation related to urate crystal deposits may be localized to a bursa or tendon sheath adjacent to the joint or may be widespread, involving multiple joint structures. Clinically, an acute gouty joint is inflamed, with overlying erythema, warmth, or both.4 Prominent periarticular inflammation may resemble cellulitis.

Calcium pyrophosphate crystal deposition is confined to hyaline cartilage, fibrocartilage, and areas of chondroid metaplasia (ie, degenerated areas of tendons, ligaments, and joint capsule) within the joint.5 Shedding of these crystals into the joint space may trigger an acute inflammatory arthritis, known as pseudogout.

Infectious arthritis

The synovium may become the seat of acute or chronic infections related to bacterial, fungal, or viral organisms.6 These infections almost always arise from blood-borne organisms and may be part of a systemic infection. The infection is based in the synovium. The cardinal pathologic findings include intense infiltration by neutrophils with resultant necrosis of the synovium and subsequent formation of granulation and scar tissue. A dense mass of fibrin, infiltrated by neutrophils, forms over the surface of the synovium. Bacterial products released within the joint are capable of producing rapid cartilage destruction.

Structural or mechanical joint derangement

Degeneration of the articular cartilage is the principal pathologic feature of osteoarthritis.7 It occurs in response to both local and host factors. Local factors include previous joint trauma (eg, meniscal tears), congenital or developmental joint alterations (eg, congenital hip dysplasia, slipped capital femoral epiphysis), alterations of the subchondral bone (eg, osteopetrosis, avascular necrosis, Paget disease), alterations of supporting structures (eg, hypermobility), and cartilage derangements (eg, ochronosis, crystal deposition). Host factors include genetic traits, obesity, and occupation. Damage to the articular cartilage is associated with subchondral bone sclerosis and marginal osteophyte formation. Patients with osteoarthritis may have an associated synovitis, with the formation of bland synovial effusions.



Two determinations serve to focus the history and physical examination of a patient with joint pain.1

The first determination is whether the pain stems from the joint or an adjacent bursa, tendon, ligament, bone, or muscle or whether it is referred from a visceral organ or nerve root. This is generally more difficult with pain in proximal, larger joints. Thus, hip pain can arise from degenerative disc disease or stenosis of the lumbar spine8 , aortoiliac occlusive disease, hip arthritis, or trochanteric bursitis.

If the pain is stemming from the joint, three broad categories of joint disease must be differentiated.9

The first category is inflammatory arthritis.10 It is characterized by inflammation affecting joint structures, such as the synovium, synovial cavity, and entheses. The second category is noninflammatory arthritis.7 This is joint disease resulting primarily from alterations in the structure or mechanics of the joint. The joint disease may occur as a result of (1) cartilage or meniscal damage with or without concomitant alterations in the structure of the subchondral bone or (2) alterations in joint anatomy as a result of congenital, developmental, metabolic, or past inflammatory diseases. The third category is arthralgia.11 Apart from joint tenderness, abnormalities of the joint cannot be identified. Such patients may have a syndrome of altered pain sensation (eg, fibromyalgia) or an early rheumatic syndrome whose clinical signs are not yet apparent or too subtle for detection (eg, arthralgias of systemic lupus erythematosus [SLE]).

These types of joint disorders may occur together in the same joint. Inflammatory joint disorders often lead to structural derangement of the joint, and, similarly, structural joint problems (eg, traumatic arthritis, osteoarthritis) often have an associated, albeit minor, inflammatory component. Finally, reports of joint pain and tenderness in any type of joint disease are influenced by the patient's emotional state and pain threshold.

  • Symptoms of joint disease
    • Pain
      • With inflammatory joint disease, the pain is present both at rest and with motion. It is worse at the beginning than at the end of usage.
      • With noninflammatory (ie, degenerative, traumatic, or mechanical) joint disease, the pain occurs mainly or only during motion and improves quickly with rest. Patients with advanced degenerative disease of the hips, spine, or knees may also have pain at rest and at night.
      • Pain that arises from small peripheral joints tends to be more accurately localized than pain arising from larger proximal joints. For example, pain arising from the hip joint may be felt in the groin or buttocks, in the anterior portion of the thigh, or in the knee.
    • Stiffness
      • Stiffness is a perceived sensation of tightness when attempting to move joints after a period of inactivity. It typically subsides over time. Its duration may serve to distinguish inflammatory from noninflammatory forms of joint disease.
      • With inflammatory arthritis, the stiffness is present upon waking and typically lasts 30-60 minutes or longer.
      • With noninflammatory arthritis, stiffness is experienced briefly (eg, 15 min) upon waking in the morning or following periods of inactivity.
    • Swelling
      • With inflammatory arthritis, joint swelling is related to synovial hypertrophy, synovial effusion, and/or inflammation of periarticular structures. The degree of swelling often varies over time.
      • With noninflammatory arthritis, the formation of osteophytes leads to bony swelling. Patients may report gnarled fingers or knobby knees. Mild degrees of soft tissue swelling do occur and are related to synovial cysts, thickening, or effusions.
    • Limitation of motion
      • Loss of joint motion may be due to structural damage, inflammation, or contracture of surrounding soft tissues.
      • Patients may report restrictions on their activities of daily living, such as fastening a bra, cutting toenails, climbing stairs, or combing hair.
    • Weakness
      • Muscle strength is often diminished around an arthritic joint as a result of disuse atrophy.
      • Weakness with pain suggests a musculoskeletal cause (eg, arthritis, tendonitis) rather than a pure myopathic or neurogenic cause.
      • Manifestations include decreased grip strength, difficulty rising from a chair or climbing stairs, and the sensation that a leg is "giving way."
    • Fatigue
      • Fatigue is usually synonymous with exhaustion and depletion of energy in patients with arthritis.
      • With inflammatory polyarthritis, the fatigue is usually noted in the afternoon or early evening.
      • With psychogenic disorders, the fatigue is often noted upon arising in the morning and is related to anxiety, muscle tension, and poor sleep.
  • Historical features important to the differential diagnoses
    • Temporal pattern of arthritis
      • The onset of symptoms can be abrupt or insidious. With an abrupt onset, joint symptoms develop over minutes to hours. This may occur in the setting of trauma, crystalline synovitis, or infection. With an insidious pattern, joint symptoms develop over weeks to months. This onset is typical of most forms of arthritis, including rheumatoid arthritis (RA) and osteoarthritis.
      • Duration of symptoms is considered either acute or chronic. Acute is less than 6 weeks in duration; chronic is 6 or more weeks in duration.
      • The temporal patterns of joint involvement are migratory, additive or simultaneous, and intermittent. With a migratory pattern, inflammation persists for only a few days in each joint (eg, acute rheumatic fever, disseminated gonococcal infection). With an additive or simultaneous pattern, inflammation persists in involved joints as new ones become affected. With an intermittent pattern, episodic involvement occurs, with intervening periods free of joint symptoms (eg, gout, pseudogout, Lyme arthritis).
    • Number of involved joints
      • Monoarthritis is the involvement of one joint.
      • Oligoarthritis is the involvement of 2-4 joints.
      • Polyarthritis is the involvement of 5 or more joints.
    • Symmetry of joint involvement
      • Symmetric arthritis is characterized by involvement of the same joints on each side of the body. This symmetry is typical of RA and SLE.
      • Asymmetric arthritis is characteristic of psoriatic arthritis, reactive arthritis (Reiter syndrome), and Lyme arthritis.
    • Distribution of affected joints
      • The distal interphalangeal joints of the fingers are usually involved in psoriatic arthritis, gout, or osteoarthritis but are usually spared in RA.
      • Joints of the lumbar spine are typically involved in ankylosing spondylitis but are spared in RA.
    • Distinctive types of musculoskeletal involvement
      • Spondyloarthropathy involves entheses, leading to heel pain (inflammation at the insertions of the Achilles tendon and/or plantar fascia), dactylitis (sausage digits), tendonitis, and back pain (sacroiliitis and vertebral disc insertions).
      • Gout commonly involves tendon sheaths and bursae, resulting in superficial inflammation.
    • Extra-articular manifestations
      • Constitutional symptoms suggest an underlying systemic disorder and are not expected in patients with degenerative joint disease. These may include fatigue, malaise, and weight loss.
      • Skin lesions may be present. Physical examination of the skin, but not the joints, may indicate the specific diagnosis of a number of rheumatic diseases. Examples include SLE, dermatomyositis, scleroderma, Lyme disease, psoriasis, Henoch-Schönlein purpura, and erythema nodosum.
      • Ocular symptoms or signs are also possible. Episcleritis and scleritis may be associated with RA or Wegener granulomatosis, anterior uveitis with ankylosing spondylitis, and iridocyclitis with juvenile RA. Conjunctivitis may be caused by reactive arthritis.


The musculoskeletal examination helps distinguish joint inflammation (eg, RA) from joint damage (eg, degenerative joint disease). It can also help elucidate the site of musculoskeletal involvement (eg, synovitis, enthesitis, tenosynovitis, bursitis) and the distribution of joint involvement.

  • Signs of inflammatory joint disease
    • Synovial hypertrophy
      • This is the most reliable sign of an inflammatory arthritis.
      • The synovial membrane is normally too thin to palpate. In a person with chronic inflammatory arthritis, the synovial membrane has a doughy or boggy consistency, a feature best appreciated at the joint line or margin.
    • Joint effusions
      • Effusions develop in response to synovial inflammation, trauma, anasarca, intra-articular hemorrhage (hemarthrosis), or an adjacent focus of acute inflammation (sympathetic effusion).
      • These are detected by performing fluid ballottement or cross-fluctuation through the synovial cavity.
    • Pain with motion, particularly at the extremes of joint motion
      • Pain throughout the whole range of motion is observed in a person with an acutely inflamed joint.
      • Pain experienced as the joint is gently forced (ie, stressed) towards its limitation of range is suggestive of synovitis.
      • Pain not present throughout the entire range of motion may indicate an extra-articular source, such as tendinitis.
    • Erythema and warmth
      • Erythema of the joint is restricted to acute inflammatory forms of arthritis, such as gout, septic arthritis, or acute rheumatic fever. It is rare in persons with RA but may occasionally occur in those with psoriatic arthritis.
      • Warmth of the joint is a sensitive sign of inflammatory arthritis and can be detected by passing the hand back and forth from the joint to a neutral area distal or proximal. Differences in warmth can also be detected by comparing the same joint on each side of the body.
    • Limited range of motion: In a person with inflammatory joint disease, limitation of motion results from the presence of a tense effusion, markedly thickened synovium, adhesions, capsular fibrosis, or pain.
    • Joint tenderness
      • This is a sensitive sign of joint disease, but it is not specific for inflammatory arthritides.
      • In an acutely inflamed joint, tenderness can be elicited over the entire synovial reflection.
      • Focal tenderness may indicate a focus of inflammation outside the joint, such as tendinitis, osteomyelitis, or fracture.
      • The presence of joint tenderness in the absence of other joint abnormalities must be interpreted in the context of the patient's emotional state.
  • Signs of degenerative or mechanical joint disease
    • Bony overgrowth of the joints (osteophytes): Those located at the distal interphalangeal joints are called Heberden nodes, while those located at the proximal interphalangeal joints are called Bouchard nodes.
    • Limited range of motion: In persons with degenerative/traumatic joint disease, the limitation of motion results from intra-articular loose bodies, osteophyte formation, or subluxation.
    • Crepitus during active or passive range of motion
      • A palpable or audible grating sensation is produced during motion of the joint.
      • Soft, fine crepitus may be felt (or heard with a stethoscope) in a rheumatoid joint when the cartilage surface is no longer smooth.
      • Coarse crepitus or grating may be felt in joints severely damaged by long-standing rheumatoid or degenerative arthritis.
    • Joint deformity: Several types must be distinguished.
      • Restriction in the normal range of motion, such as a lack of full joint extension that results in a flexion deformity, is one type.
      • Another is malalignment of the articulating bones, such as ulnar deviation of the fingers or valgus deformity of the knee.
      • The third type is an alteration in the relationship of the two articulating surfaces, such as subluxation (ie, some contact between the two articulating surfaces) and dislocation (ie, complete loss of contact between the two articulating surfaces).
  • Techniques of the musculoskeletal examination
    • Inspection
      • Each joint has a characteristic or normal appearance, and each assumes a characteristic resting position.
      • Compare one side of the body with the other in order to detect joint abnormalities, including swelling, deformity, overlying erythema, or wasting of the periarticular musculature.
      • With a sagittal view of the patient, take note of joint deformities that result from the lack of full extension of a joint (eg, flexion deformities).
      • With a coronal view of the patient, take note of joint malalignment, which may result in valgus or varus deformities.
    • Palpation
      • Palpation of the joints is used to assess for signs of inflammation (eg, warmth, synovial hypertrophy, joint effusion, tenderness) and for signs of joint damage (eg, bony swelling, crepitus).
      • The examiner should palpate with enough pressure to blanch his or her thumbnail. This ensures that the assessment of joint tenderness is uniform. The application of this amount of force during palpation should not cause pain in a normal joint.
    • Assessment of range of motion
      • Assess limitation of passive motion by comparing it with the expected range of motion observed in healthy individuals and with the range of motion in the contralateral joint.
      • Active range of motion can be used to assess the presence of pathology in juxta-articular structures, such as tendons and bursae.
      • Pain occurring during only a portion of the range of motion may be related to an extra-articular structure, such as a tendon or bursa.
      • Assess pain with joint motion; observe the patient's face for wincing.
      • Assess crepitus by palpating the joint with one hand while moving the joint passively with the other. In the lower extremities, crepitus of the hip or knee can sometimes be heard as the patient arises from a chair, climbs a step, or pivots on the affected joint.
      • Assess instability or abnormal mobility by applying forces to the relaxed joint in planes of motion normally associated with little or no motion. Instability of a lower extremity joint (eg, knee, ankle) should also be assessed by observing the joint during weight-bearing and walking. Instability of the joint may be due to laxity of ligaments or destruction of the articular surface.
  • Examination techniques useful for detection of arthritis in specific joints
    • Hands
      • To detect synovial effusions in interphalangeal joints, gently squeeze the superolateral joint lines with the thumb and index finger while palpating the volar and dorsal sides with the opposite thumb and finger. Use the fingers to detect a ballooning effect as pressure is applied to the joint.
      • To detect metacarpophalangeal (MCP) joint synovitis, gently squeeze the dorsal aspects of the fully extended MCP joint distally with the thumb and index finger of one hand while screening for a ballooning effect with the same fingers of the opposite hand placed over the proximal aspects of the joint.
      • To assess grip strength, the patient is asked to squeeze two adjacent fingers of the examiner with maximum force.
    • Wrists
      • For wrist assessment, support the wrist in 15° flexion. Palpate the dorsal aspect of the radiocarpal and ulnocarpal joints for a spongy consistency, which is indicative of synovial hypertrophy.
      • Percuss over the volar aspect of the wrist; elicitation of paresthesias in the median nerve distribution is indicative of carpal tunnel syndrome.
    • Elbows
      • Assess for flexion deformity (ie, inability to fully extend); this may be an early sign of an inflammatory arthritis.
      • Palpate for soft tissue swelling of synovitis in fossae between the olecranon and lateral or medial epicondyles.
      • Assess for subcutaneous nodules in olecranon bursae and over the extensor surfaces of the elbow and forearm; these may represent rheumatoid nodules or tophi.
    • Shoulders
      • Evaluate the function of the entire shoulder complex. Observe the patient abduct both arms from 0° along side the body to 180° straight up. Assess external rotation by noting the position behind the neck or head to which the patient's hands can reach from above. Assess internal rotation by noting the highest level the dorsum of the patient's hands can reach in the back from below. A limitation of active shoulder motion should prompt an evaluation of passive motion.
      • Isolate and assess the motion of the glenohumeral joint. Abduction is checked with the patient's scapula fixed in place and the elbow flexed. The examiner uses one hand to prevent the spine or tip of the scapula from moving and then uses the other hand to abduct the patient's flexed arm. Normal glenohumeral abduction is 90°. External rotation is a movement mediated solely by the glenohumeral joint. It can be assessed by externally rotating the arm, flexed to 90° at the elbow and positioned either with the arm at the patient's side or in 90° of abduction. Limitation of glenohumeral motion is an indication of glenohumeral joint arthritis or capsular fibrosis.
      • Assess rotator cuff function. Observe the patient actively abduct the arm. Pain experienced at 60-100° of active abduction is an indication of supraspinatus tendonitis and/or subacromial bursitis.12
      • Spine: Assess the range of motion of the entire spine (ie, cervical, thoracic, lumbar).
      • For the cervical spine, ask the patient to touch the chin to the chest (flexion) and then look up at the ceiling (extension). For lateral flexion, ask the patients to touch an ear to their shoulder. For lateral rotation, ask patients to touch their chin to a shoulder. During lateral rotation and flexion, pain that occurs on the ipsilateral side of the neck is bony in origin (eg, apophyseal joint disease), while pain on the contralateral side is muscular or ligamentous in origin.
      • With the thoracic spine, restriction of chest expansion is a sign of ankylosing spondylitis. The circumference of the chest should be measured at the level of the nipples. A difference of less than 2.5 cm with inspiration is clearly abnormal.
      • For the lumbar spine, assess flexion, extension, and lateral flexion.13 Pain upon extension suggests pathology in the posterior elements of the spine (eg, facet joints or neurogenic compression seen with spinal stenosis). Pain upon flexion suggests disc disease. Lateral flexion is restricted early in the course of ankylosing spondylitis. Lumbar spine flexion is measured reproducibly with the Schober test. With the patient erect, make a horizontal mark at the level of the sacral dimples and make a second mark over the spine at a distance 10 cm above the first mark. Have the patient bend forward in an attempt to touch the floor. The distance between the 2 marks is measured in flexion. Normally, the distance should increase from 10 cm to more than 15 cm. Restriction of lumbar spine flexion can be seen with muscle spasm and ankylosing spondylitis. More severe restriction of motion (eg, result less then 2 cm) without acute lumbar pain is a reliable sign of ankylosing spondylitis.
      • Hips
      • Perform the log-rolling test. With the patient's leg in extension, the examiner gently rolls the entire limb back and forth. Limitation of internal or external rotation (particularly when compared to the contralateral hip) or groin pain is suggestive of true hip pathology.
      • The Thomas test helps assess for hip flexion deformity. The opposite hip is fully flexed as a means to flatten the lumbar lordosis and fix the pelvis. If the knee of the involved side is observed to elevate off the examining table, then an ipsilateral hip flexion deformity is present. This may be an indication of hip arthritis or tight hip flexor muscles.
      • For the Trendelenburg test, the patient is asked to stand and bear weight on only the involved leg. If the contralateral pelvis drops below level, then weakness of the hip abductors (ie, gluteus medius) is present on the affected side. Weakness of the hip abductors is a sign of hip arthritis. It can also have a neurogenic (eg, L5 root disease) or myogenic cause.
    • Knees14
      • Assess for synovitis. Visually inspect the knee for swelling and erythema; compare the affected knee with the contralateral knee. Palpate for warmth. Compare the temperature of the affected knee with that of the contralateral knee. The examiner should gently pass his or her hand from the patient's mid thigh or mid calf to the knee, assessing for a warmer temperature over the knee.
      • Assess for synovial effusion by eliciting the bulge sign and performing ballottement. The bulge sign test is performed with the patient supine, quadriceps relaxed, and knee fully extended. A small effusion, if present, is displaced from the medial side of the knee by stroking with the examiner's thumb. Its return is facilitated by quickly tapping the lateral side with the ends of the examiner's fingers and is observed as a gradual filling out of the recess created by stroking. Repeat the process several times in quick succession to be confident of the result. Ballottement is useful for detecting large knee effusions. With the patient's knee relaxed and fully extended, cup both hands around the knee, bringing the knee effusion into the central portion of the synovial cavity. Using the right index finger, push the patella straight down and release it quickly. The presence of a patellar tap, felt as the patella knocks against the underlying femoral condyles, is indicative of an effusion.
      • Assess range of motion. Synovitis with or without a synovial effusion may result in a decrease in the range of motion, including a loss of full extension (flexion deformity) and/or a reduction in flexion.
      • Assess for joint damage. Palpate the knee for crepitus with passive movement. Palpate the patella for crepitus as the patient actively extends the knee from a flexed position.
      • Assess for joint laxity. Test for lateral instability by attempting to adduct and abduct the lower leg with the knee held in 15° of flexion. Test for anteroposterior instability by attempting to push and pull the lower leg backward and forward with the knee held in 30° of flexion (Lachman test). Observe the alignment of the knee with the patient standing and bearing weight on both knees. Observe the back of the knee for popliteal or Baker cysts.
    • Ankles
      • Palpate for tenderness and soft tissue swelling over talar, subtalar, and midtarsal joints.
      • Assess range of motion of the talar (ie, with dorsiflexion, plantar flexion) and subtalar (ie, with inversion, eversion) joints.
    • Feet
      • Squeeze the row of metatarsophalangeal joints, assessing for the presence of pain or tenderness.
      • Palpate the small joints of the feet, assessing for the presence of tenderness, bony or soft tissue swelling, or joint effusion.

Differential Diagnoses

Other Problems to Be

  • Acute monoarthritis15
    Septic Arthritis16
    Gout and Pseudogout4
    Systemic rheumatic disease manifesting as monoarticular involvement
    Juxta-articular fracture
    Chronic monoarthritis
    Chronic infectious arthritis (see Septic Arthritis)
    Lyme Disease
    Crystalline synovitis (see Gout and Pseudogout)
    Pauciarticular juvenile rheumatoid arthritis (RA; see Rheumatoid Arthritis)
    Systemic rheumatic disease presenting with monoarticular involvement
    Ischemic necrosis (see Avascular Necrosis)
    Paget disease involving the joint (see Paget Disease)
    Stress Fracture
    Metastatic tumor
    Synovial osteochondromatosis
  • Acute polyarthritis
    Rheumatic fever (see Acute Rheumatic Fever)
    Gonococcal Arthritis
    Polyarticular gout (see Gout)
    Polyarticular pseudogout
    Viral arthritis (eg, hepatitis B infection, parvovirus B-19 infection)
    Bacterial endocarditis (see Infective Endocarditis)
    Rheumatoid Arthritis
    Still disease
    Systemic Lupus Erythematosus17
    Reactive Arthritis18
    Acute sarcoid arthritis
    Mediterranean Fever, Familial
    Enteropathic Arthropathies
  • Chronic polyarthritis
  • Shoulder
    • Referred pain
      • This is inflammation of the rotator cuff tendons, arising acutely as a result of a recognizable injury (throwing) or insidiously as a result of repeated impingement on the overlying acromion, coracoacromial ligament, acromioclavicular joint, or coracoid.
      • The principal symptom is pain in the deltoid region of the shoulder, aggravated by an overhead motion of the arm. The patient may also describe shoulder pain when sleeping on the affected side.
      • Examination findings include (1) tenderness in the subacromial region, between the greater tubercle of the humerus and acromial process; (2) pain in the mid arc of active abduction, usually 60-120°; (3) reproduction of pain when midarc abduction and external rotation are resisted isometrically; and (4) range of passive shoulder abduction exceeding that of active abduction.
      • Treatment includes avoidance of overhead reaching, nonsteroidal anti-inflammatory drugs (NSAIDs) for 2-3 weeks, and physical therapy with stretching and strengthening exercises. Subacromial corticosteroid injections may be used if symptoms do not improve.
    • Rotator cuff tear (see Rotator Cuff Injuries)
      • These are transverse or longitudinal tears of the supraspinatus or infraspinatus tendons. They occur at the musculotendinous juncture, approximately 1 cm from their insertion on the humerus.
      • They may arise as a result of an acute injury (eg, fall on an outstretched arm, hyperabduction, fall onto the side of the shoulder) or gradual attrition in the setting of chronic rotator cuff tendonitis.
      • With acute injury, symptoms include sharp shoulder pain followed by weakness of abduction. In the setting of chronic rotator cuff tendonitis, a tear is signaled by weakness of abduction or loss of smooth motion during abduction.
      • Examination findings include weakness and pain in the mid arc of abduction and external rotation and a loss of smooth overhead reaching (partial tear) or an inability to reach overhead (complete tear).
      • Initial management is conservative. Young patients with acute tears should be evaluated by an orthopedic surgeon.
    • Bicipital Tendonitis
      • This is inflammation of the long head of the biceps muscle as it passes through the bicipital groove of the anterior humerus.
      • It usually arises as a result of overuse with activities that require repetitive lifting.
      • The primary symptom is pain in the anterior aspect of the shoulder (over the humeral head), which is aggravated by lifting or overhead pushing or pulling.
      • Examination findings include tenderness of the bicipital groove and pain aggravated by isometric resistance to elbow flexion or supination of the arm flexed to 90°.
      • Treatment includes elimination of lifting, avoidance of over-the-shoulder reaching, and NSAIDs for 3-4 weeks. A corticosteroid injection of the bicipital groove can be given if symptoms persist.
    • Subacromial bursitis
      • This is the accumulation of fluid within the subacromial bursa, arising as a result of rotator cuff tendonitis. Significant fluid may be detected during a physical examination.
      • Treatment is similar to that for rotator cuff tendonitis. A significant effusion can be drained, followed by corticosteroid instillation.
    • Frozen shoulder (adhesive capsulitis)
      • This refers to conditions in which the range of motion of the glenohumeral joint is significantly reduced as a result of pathology within the joint capsule.
      • Primary symptoms are pain and gradual loss of shoulder motion without any known injury.
      • Associated medical conditions include diabetes mellitus, recent myocardial infarction, stroke, recent neurosurgical procedure, Parkinson disease, and hypothyroidism.
      • Examination findings include a reduced range of motion during both active and passive motion. Pain is present particularly at the extreme ranges of motion.
      • Radiographic images do not show evidence of glenohumeral arthritis.
      • The initial treatment regimen includes NSAIDs, nonnarcotic analgesics, and physical therapy. Occasionally, a 2- to 4-week course of oral corticosteroids combined with aggressive physical therapy may result in decreased pain and increased shoulder motion.
    • Acromioclavicular syndrome (see Acromioclavicular Joint Injury)
      • Pain arises from the acromioclavicular joint as a result of arthritis or injury to the acromioclavicular ligaments.
      • Osteoarthritis of the acromioclavicular joint with inferior osteophytes can lead to rotator cuff impingement and associated tendonitis.
      • This injury may be acute or chronic, and patients may report a history of trauma (eg, fall during a contact sport).
      • Examination findings include tenderness and swelling of the acromioclavicular joint. Deformity of the joint may result from subluxation.
      • Pain in the joint is aggravated by downward traction of the ipsilateral arm or forced passive adduction.
      • An acute acromioclavicular injury is treated with a shoulder immobilizer.
  • Elbow, wrist, and hand
    • Lateral Epicondylitis (tennis elbow)
      • This is the most common cause of elbow pain.
      • Pain is felt along the lateral aspect of the elbow.
      • Tenderness is present over the lateral epicondyle at the attachment of the extensor tendons of the forearm.
      • Resisting wrist dorsiflexion with the elbow in extension produces increased pain. Elbow extension is normal.
      • Treatment includes rest, NSAIDs, and local steroid injections.
    • Medial Epicondylitis(golfer elbow)
      • This condition is less common than lateral epicondylitis.
      • Resisted wrist flexion with the elbow in extension produces pain.
      • Tenderness may occur at the insertion of the common flexor tendon at the medial epicondyle.
    • Olecranon Bursitis
      • The anatomically superficial position of this bursa predisposes it to injury and inflammation.
      • The patient reports pain when leaning on the elbow and during flexion.
      • Examination findings include tenderness at the tip of the olecranon process and an occasional friction rub. Visible swelling of the bursa may be evident. In acute cases, warmth and erythema are present.
      • Acute bursitis must undergo aspiration for culture and crystal examination.
    • De Quervain Tenosynovitis
      • This is a stenosing tenosynovitis of the abductor pollicis longus and extensor pollicis brevis tendons, resulting from repetitive motion or overuse.
      • Pain is noted along the radial aspect of the wrist and thumb during pinching, grasping, and similar movements.
      • Ulnar deviation of the wrist, with the thumb held in abduction by the flexed fingers of the same hand (Finkelstein test) reproduces the pain. Crepitus of the tendons may be evident.
      • Treatment includes use of a thumb spica splint, avoidance of repetitive thumb flexion or abduction, and NSAIDs.
    • Trigger finger and trigger thumb (see Trigger Finger)
      • This condition is also known as stenosing digital tenosynovitis, snapping finger, and snapping thumb.
      • Injury is the result of overuse.
      • Examination findings include pain and tenderness and snapping, triggering, or catching during movement of the finger or thumb. A nodule is felt in the palm on the flexor tendon just proximal to the digital-palmar crease.
  • Hip
    • Referred pain
      • Pain in the posterior aspect of the hip is often referred from the lumbar spine.
      • Sacroiliac disorders can also cause buttock pain.
      • Pain from arthritis of the thoracolumbar junction may be referred pain to the area of the greater trochanters and may mimic trochanteric bursitis.
      • Radiculopathies of the L2-L4 nerve roots may produce pain in the inguinal area and the anterior aspect of the thigh. This may mimic hip disease.
      • Iliopsoas abscesses, retroperitoneal appendicitis, tuberculous abscesses, or pelvic inflammatory disease can be a cause of pain in the hip region.
      • Thrombosis or aneurysm formation in the branches of the aorta or iliac vessels may produce buttock, thigh, or leg pain that may be confused with hip pain.
      • True intra-articular hip pain is most often felt in the groin and anterior thigh. Occasionally, hip disease can manifest with isolated knee pain.
    • Trochanteric Bursitis
      • This is the most common cause of pain in the hip region (felt over the lateral aspect of the hip).
      • Pain increases with activities such as walking, squatting, and climbing stairs; pain typically decreases at rest. Patients note increased pain when lying on their ipsilateral side. The pain may be associated with a limp.
      • The area over the greater trochanter may be tender and boggy. Resisted abduction of the hip reproduces the pain.
      • Local corticosteroids with anesthetics may help.
    • Iliopsoas bursitis
      • This condition can occur in patients with osteoarthritis, RA, pigmented villonodular synovitis, osteonecrosis, and septic arthritis.
      • Most patients are asymptomatic or present with a painful inguinal mass.
      • CT scan is the best diagnostic test.
      • The instillation of corticosteroids is effective therapy.
    • Ischiogluteal bursitis
      • This occurs most commonly in patients with occupations that favor repeated friction of the ischial bursa.
      • Patients note pain over the ischial tuberosities; the pain is aggravated by sitting and lying down.
      • Local tenderness of the ischial tuberosities is found upon palpation
      • Symptoms may be alleviated by avoiding pressure or friction on the ischial tuberosities (ie, with the use of doughnut-shaped cushions) and local instillation of corticosteroids.
    • Adductor tendinitis
      • This disorder occurs in patients engaged in sports activities that involve straddling (eg, horseback riding, gymnastics, dancing).
      • Pain is typically felt in the groin and inner aspect of the thigh.
      • Tenderness can be elicited by local palpation of the adductor muscles, especially near their insertion on the front of the pelvis. Pain is increased by passive abduction of the thighs and active adduction against resistance.
      • Treatment consists of rest and ice packs during the acute phase. NSAIDs, ultrasonography, and progressive stretching exercises are used in the subacute phase.
      • Local corticosteroid injections are reserved for patients resistant to these conservative modalities.
  • Knee and ankle
    • Prepatellar Bursitis (housemaid knee)
      • This condition is related to recurrent trauma and usually occurs in persons who spend significant time kneeling.
      • In chronic cases, a well-circumscribed area of fluctuance is present over the prepatellar area. In acute cases, warmth, edema, and erythema are noted over the anterior knee. Fluctuance may be subtler. Tenderness is maximal over the prepatellar bursa. Knee flexion increases the pain, whereas knee extension does not. A joint effusion, if present, is small.
      • Etiologies include trauma, gout, and infection.
      • Aspiration of acute bursitis is necessary to assess for the presence of an infection or crystals.
      • Traumatic bursitis improves with rest and avoidance of kneeling.
    • Anserine bursitis (see Pes Anserinus Bursitis)
      • Pain is noted over the medial aspect of the knee, is made worse by climbing stairs, and is often present at night.
      • It is most common in overweight women with osteoarthritis of the knees.
      • Examination reveals exquisite tenderness over the anserine bursa, located over the medial aspect of the knee approximately 2 inches below the joint line.
      • Treatment includes a corticosteroid injection into the bursa and an exercise regimen to stretch the adductor and quadriceps muscles.
    • Patellar tendonitis (jumper's knee)
      • Most commonly, this affects young athletes who are engaged in sports that require repetitive running, kicking, and jumping.
      • Pain is noted at the inferior pole of the patella during activities such as climbing stairs, running, and jumping.
      • Treatment consists of rest, NSAIDs, knee bracing, and an exercise regimen to stretch and strengthen the quadriceps and hamstring muscles.
    • Achilles tendonitis (see Achilles Tendon Injuries and Tendonitis)
      • Pain, swelling, tenderness, and crepitus are noted over the tendon near its insertion.
      • This form of tendonitis is usually caused by repetitive trauma and microscopic tears due to excessive use of the calf muscles in ballet dancing, distance running, basketball, jumping, and other athletic activities. Faulty footwear with a rigid shoe counter also may produce Achilles tendonitis.
      • Examination findings include thickening and irregularity of the tissues surrounding the tendon and palpable nodule(s) within the tendon (occasionally representing xanthomata, tophi, or rheumatoid nodules). Passive dorsiflexion of the ankle intensifies the pain.
      • Abnormalities of the tendon and peritendinous tissues can be demonstrated on images from ultrasonography and MRI studies.
      • Treatment consists of rest, avoidance of the provocative occupational or athletic activity, shoe modification, a heel lift to reduce tendon stretching during walking, and NSAIDs. Physical therapy includes local heat application, gentle stretching exercises, and a temporary splint with slight plantar flexion.
    • Retrocalcaneal bursitis (see Achilles Tendon Injuries and Tendonitis)
      • This is inflammation of the retrocalcaneal bursa, resulting in pain and tenderness at the back of the heel.
      • The area anterior to the Achilles tendon and posterior to the calcaneus is tender; passive dorsiflexion of the ankle produces pain.
      • Bursal distension is palpable and produces bulging on both sides of the tendon.
      • This may occur as a result of repetitive trauma or as a manifestation of gout or a systemic inflammatory arthritis.
      • Diagnosis can be confirmed based on radiography (obliteration of the retrocalcaneal recess), ultrasonography, or MRI findings.
      • Rest, activity modification, moist heat application, slight heel elevation using a felt heel pad, and NSAIDs constitute sufficient therapy for most patients.
      • A walking cast or cautious corticosteroid injection into the bursa is sometimes required.


Laboratory Studies

  • Most useful diagnostic tests for specific rheumatic diseases20
    • Septic arthritis: Order a Gram stain and culture of synovial fluid.6,21
    • Gout or pseudogout: Use compensated polarized light microscopy to examine a drop of synovial fluid for intracellular urate (gout) or calcium pyrophosphate dihydrate (pseudogout) crystals.
    • Ankylosing spondylitis: Obtain sacroiliac joint radiographs to demonstrate bilateral sacroiliitis.22
    • Osteoarthritis: Obtain radiographic images of the affected joint.
    • Systemic lupus erythematosus (SLE): Screen with an antinuclear antibody (ANA) test. If positive, test for Smith (Sm) and double-stranded DNA antibodies. These antibodies are more specific for SLE but are present in only 30-60% of patients with SLE, respectively.23
  • Screening tests for all types of inflammatory arthritis24
    • Erythrocyte sedimentation rate (ESR): In the setting of joint pain and equivocal joint examination findings, an elevated ESR supports the presence of an inflammatory arthritis.
    • C-reactive protein (CRP): This test is a nonspecific measure of inflammation and is an alternative to obtaining the ESR. In contrast to the ESR, the CRP level (1) can be measured on frozen serum, (2) is not influenced by the presence of anemia or hyperglobulinemia, (3) rises more rapidly in response to an inflammatory stimulus, and (4) may require more time for the laboratory result to be available (ie, 1 h for ESR; >24 h for CRP).
    • Rheumatoid factor and cyclic citrullinated peptide (CCP): A rheumatoid factor test should be obtained when rheumatoid arthritis (RA) is at least moderately possible in the patient. Results may be positive in up to 20% of healthy elderly persons and in persons with other rheumatic diseases (eg, SLE, Sjögren syndrome, vasculitis), chronic infections (eg, subacute bacterial endocarditis, hepatitis C), chronic liver disease, or chronic lung disease. Measuring antibodies to CCP is a new test for RA; it has higher specificity but lower sensitivity than rheumatoid factor. The CCP antibody test is particularly useful in the evaluation of a patient with joint pain whose rheumatoid factor is of low titer and whose findings on joint examination are not definitive for synovitis.
    • ANAs: ANA tests are commonly obtained in patients with arthralgias or arthritis as a screening test for SLE or another connective-tissue disorder.23 More than 95% of patients with SLE have ANAs; thus, a negative ANA result is a strong indicator that SLE is not present. However, a positive ANA result lacks specificity and may occur in persons with other connective-tissue diseases or certain medical illnesses or in 5-10% of otherwise healthy individuals. The diagnostic yield of the ANA test is increased substantially when the patient has features that suggest a diagnosis of SLE or another autoimmune disease in addition to joint pain. These include a photosensitive skin rash, pleuritis, pericarditis, Raynaud phenomenon, constitutional symptoms (eg, fever), leukopenia, thrombocytopenia, sicca symptoms, and proteinuria.
  • Screening tests for acute polyarthritis
    • Blood cultures
    • Antistreptolysin O titer
    • Parvovirus B-19 immunoglobulin G and immunoglobulin M levels
    • Hepatitis B serology
    • ANAs
    • Others to consider: These may include an HIV test, a rubella titer, an angiotensin-converting enzyme level and chest radiograph, and antineutrophil cytoplasmic antibody testing.
  • Screening tests for chronic polyarthritis
    • Complete blood cell count
    • ESR and CRP level
    • ANAs
    • Rheumatoid factor and CCP antibody
    • Chemistry profile, including liver function tests and a serum creatinine level
    • Serum uric acid level
    • Urinalysis
    • Others to consider: These include a thyroid-stimulating hormone level, a serum ferritin level, and an iron saturation of serum transferrin.
  • Screening tests for diffuse arthralgias and myalgias
    • ESR and CRP level to exclude inflammatory disease, including polymyalgia rheumatica
    • Creatine kinase and aldolase level to exclude myositis
    • Thyroid testing
    • Chemistry profile (ie, calcium, phosphorus, electrolyte, glucose, total protein) to exclude metabolic or endocrine disorders
    • Others to consider: These include a 25-hydroxy vitamin D level (in elderly housebound individuals to exclude osteomalacia), sacroiliac joint radiography (to exclude ankylosing spondylitis, especially in woman <45>

Imaging Studies

  • Choice of imaging modality
    • Plain radiography: This is the least expensive imaging modality and is most useful for clarifying the nature of joint abnormalities already noted during the physical examination (eg, swelling [bony vs soft tissue], loss of motion [bony vs soft tissue], instability [ligamentous vs destruction of articular surface], focal bony tenderness [fracture vs osteomyelitis]).25 The appearance of joints on plain radiographs is often distinctive for various forms of arthritis (see Plain radiographic findings in various arthritides, although these characteristic changes may not be apparent early in the disease course. Plain radiographs are useful for monitoring the progression of chronic arthritides (eg, osteoarthritis, RA).
    • CT scan: This technique obtains cross-sectional images of skeletal structures.26 It is most useful for (1) assessing trauma of the spine and pelvis, (2) evaluating arthritis in axial joints (eg, sacroiliac, atlantoaxial, sternoclavicular), (3) evaluating pain in complex joints in which overlying structures obscure plain radiography views (eg, ankle, wrist, temporomandibular joints), and (4) evaluating degenerative disc disease of the spine and possible disc herniations.
    • MRI: This imaging modality is the best for assessing soft tissue and spinal cord elements.26 It is of greatest use for assessing rotator cuff tears, spinal stenosis, ligamentous or meniscal abnormalities of the knee and wrist joints, osteonecrosis (ie, avascular necrosis of bone), stress fractures, osteomyelitis, and subchondral bone injury in osteoarthritis or meniscal tears.
    • Arthrography: It is of greatest use for defining abnormal communication between the synovial space and adjacent bursae and soft tissue (ie, popliteal cysts, rupture of rotator cuff with communication between glenohumeral joint space and subacromial bursa).
    • Radionuclide bone scanning: This is widely available, and the cost is comparable to that of a CT scan. It is most useful for assessing osteomyelitis, stress fractures, and bony metastasis. It may be used to exclude skeletal disease in patients with diffuse musculoskeletal pain.
  • Plain radiographic findings in various arthritides22
    • Rheumatoid arthritis
      • Early changes include soft tissue swelling and periarticular demineralization.
      • Later changes include uniform loss of joint space (indicative of diffuse cartilage loss) and bony erosions (initially along joint margins where intra-articular bone is not covered by cartilage).
      • Advanced changes include diffuse bony erosions, joint subluxation, and foreshortening of digits. Ankylosis of joints is rare.
    • Psoriatic arthritis
      • Early changes include soft tissue swelling, occasionally involving the entire digit (ie, sausage digit), and an absence of periarticular demineralization.
      • Later changes include erosions coupled with reactive new bone formation, initially at joint margins and later within the center of the joint. Other late changes are uniform joint space narrowing and ankylosis of involved joints.
      • Advanced changes are joint space widening in interphalangeal joints caused by severe destruction of marginal and subchondral bone, resorption of tufts of distal phalanges of fingers and toes, arthritis mutilans (ie, severe joint destruction with extensive bone resorption), and the pencil-in-cup deformity.
      • Distinctive features are involvement of the distal interphalangeal joints, a tendency for early ankylosis, asymmetric joint involvement, and abnormalities of phalangeal tufts.
    • Reactive arthritis
      • Radiographic features are similar to psoriatic arthritis, but they are often less severe and have a predilection for lower extremity joints.
      • Distinctive features include a predilection for lower extremities (eg, knees, ankles, feet), a tendency for unilateral or asymmetric sacroiliitis, paravertebral ossification, and calcaneal erosions and/or periostitis at sites of Achilles tendon and plantar fascia insertion.
    • Gout
      • Acute gouty arthritis is indicated by soft tissue swelling. Degenerative changes of the involved joint are common.
      • Intercritical gout does not manifest radiographic abnormalities, apart from possible degenerative changes in the joint.
      • Chronic tophaceous gout is indicated by soft tissue swelling, often asymmetric or outlining an eccentric nodular subcutaneous mass. The joint space may be preserved despite extensive erosions, a finding not expected in RA. Bone erosions are contiguous with tophi and are characterized by overhanging and sclerotic margins. Osteolytic bone lesions occur near joints. Periarticular demineralization is absent or mild, except late in the disease course.
    • Calcium pyrophosphate dihydrate crystal deposition disease
      • Radiographic evidence of calcium crystal deposition in articular structures is seen most often in the knee, symphysis pubis, wrist, elbow, and hip. The prevalence increases with age, and it is often an incidental finding and not often associated with joint symptoms. Hyaline cartilage calcification is fine and linear, and it follows the contour of the underlying subchondral bone. Fibrocartilage calcification is coarse and irregular, and it is often seen in knee menisci, triangular fibrocartilage and the meniscus of the wrist, and the symphysis pubis. Synovial calcification is amorphous and usually occurs at sites of synovial reflection. Capsular calcification is linear deposits bridging the peripheral joint margins. Extra-articular calcification occurs in tendons, ligaments, and para-articular soft tissues.
      • Pyrophosphate arthropathy is a distinctive arthropathy that may occur in patients with calcium pyrophosphate dihydrate crystal deposition disease. Radiographic findings are the same as those for osteoarthritis. Distinctive features include (1) involvement of joints not usually affected by osteoarthritis (eg, MCP, wrist, elbow, ankle, shoulder), (2) involvement of specific joint compartments (eg, radiocarpal and trapezioscaphoid joints of wrists, patellofemoral joint of knee, talocalcaneonavicular joint of midfoot), (3) prominent subchondral cysts, and (4) occasional articular destruction (resembling a neuropathic joint) with subchondral bone collapse and fragmentation and formation of intra-articular loose bodies.
    • Infectious arthritis
      • Early changes include symmetric soft tissue swelling, an absence of periarticular demineralization in an acute pyogenic arthritis, and joint space loss (although joint space widening may be seen initially because of fluid accumulation in a small joint space).
      • Later changes include marginal bone erosions. Also, the continuous white cortical line that normally defines the margin of articulating bone is lost; these changes are expected on both sides of the joint. A periosteal reaction occurs. Finally, gas formation within the joint and adjacent soft tissues can be seen with infections related to Escherichia coli, Enterobacter liquefaciens, and Clostridium perfringens.
      • Advanced changes include destruction of subchondral bone, intra-articular bony ankylosis, and subluxation or dislocation.
    • Osteoarthritis
      • Early changes include small osteophytes at joint margins, focal narrowing of joint spaces (more uniform joint space loss is noted in interphalangeal and MCP joints of the hands and sacroiliac joints), subchondral bony sclerosis in the segment affected by joint space loss, and an absence of periarticular demineralization.
      • Later changes include large and more extensive osteophytes at joint margins or at ligamentous attachments (eg, tibial spines), more pronounced focal joint space narrowing, subchondral bone cysts with sclerotic margins in the areas of joints affected by joint space loss, and the formation of bony ossicles (round or oval fragments of bone) in soft tissues adjacent to the joint or within the joint cavity.
      • Advanced changes include extensive joint space loss and joint deformity.

Other Tests

  • Synovial fluid analysis27
    • This test is used to broadly characterize the type of arthritis, to identify crystals, and to establish the diagnosis of septic arthritis and crystal-induced synovitis.27
    • Synovial fluid types are classified as normal, noninflammatory, inflammatory, septic, or hemorrhagic.
      • Normal: Characteristics include clear to pale yellow color, transparent clarity, WBC count of less than 200/µL with less than 25% polymorphonuclear (PMN) leukocytes, and very high viscosity.
      • Noninflammatory (group I): Characteristics include pale yellow color, transparent clarity, WBC count of 200-2000/µL with less than 25% PMN leukocytes, and high viscosity. It typifies osteoarthritis, traumatic arthritis, and an early or resolving stage of an inflammatory arthritis.
      • Inflammatory (group II): Characteristics include yellow-to-white color, translucent-to-opaque clarity, WBC count of 2000-50,000/µL with more than 70% PMN leukocytes, and low viscosity. It typifies RA and other chronic inflammatory arthritides.
      • Septic (group III): Characteristics include a white-to-cream color, opaque clarity, WBC count of more than 50,000/µL with more than 90% PMN leukocytes, and very low viscosity. It typifies bacterial arthritis, but it also may occasionally be seen in crystalline arthritis and flares of RA.
      • Hemorrhagic (group IV): Characteristics include a hemorrhagic color and opaque clarity. Fat globules should be sought in hemorrhagic fluids by centrifuging the synovial fluid. A supernatant of fat is indicative of a juxta-articular fracture.
    • A joint may be affected by more than a single process; thus, septic arthritis and gout or pseudogout may coexist in the same joint.
    • The synovial fluid WBC count may be lower in patients who are early in the course of septic arthritis or in patients with disseminated gonococcal infection.
    • Crystal analysis requires compensated polarized light microscopy, which is available in most diagnostic or pathologic laboratories.28 It is performed on a wet smear preparation of synovial fluid. Intracellular crystals in synovial fluid are required to establish a diagnosis of acute gout or pseudogout. Urate crystals are needle-shaped with strong negative birefringence. Calcium pyrophosphate dihydrate crystals are rhomboid-shaped with weak positive birefringence. Urate crystals appear yellow and calcium pyrophosphate dihydrate crystals appear blue when their long axes are aligned parallel to that of the red compensator filter.


  • In the majority of patients with rheumatic diseases, an accurate diagnosis can be established without performing a synovial biopsy. For certain conditions, histopathologic findings in the synovium are either pathognomonic or highly specific. These include various granulomatous arthritides (eg, tuberculous, fungal, sarcoidosis), amyloidosis, synovial tumors, ochronosis, hemochromatosis, and multicentric reticulohistiocytosis.
  • Medical Care
    Most patients who present with a new musculoskeletal complaint have a problem restricted to one anatomic region or joint. Examples include back or shoulder pain. These problems are usually recognized as self-limited and not of the type to pose a major hazard to the health of the patient. Such patients are treated symptomatically and advised about the optimal balance of activity and rest, the benign nature of the problem, and the expectation of healing in 2-6 weeks. Extensive testing is inappropriate because abnormalities may be revealed that are irrelevant, and these results may prompt further, often unnecessary, investigations. Clinical situations in which acute musculoskeletal symptoms must be evaluated promptly and thoroughly include (1) a severe condition involving one joint or, at most, a few joints; (2) a patient who is febrile, is systemically ill, or is showing signs of multiple organ involvement; (3) a problem associated with significant trauma; and (4) a condition in which an associated neurologic problem exists, such as carpal tunnel syndrome, sciatica, or cervical radicular symptoms.9

    In patients with arthritis, the goals of treatment include relief of pain, restoration or maintenance of joint function, and prevention of joint damage. These goals are achieved with both pharmacologic and nonpharmacologic therapeutic modalities. While some modalities are common to the treatment of all forms of arthritis, others are specific to certain forms of arthritis. Thus, proper treatment begins with an accurate diagnosis. One of the challenges in treating arthritis is determining the expected prognosis and instituting appropriate therapy in a timely fashion, thereby avoiding the development of irreversible joint dysfunction.

    The initial assessment of the patient should allow classification of the joint problem into one of the categories detailed below:

    Acute monoarthritis21,15
    Principles of management
    Hospitalize any patient with possible septic arthritis.
    Aspiration of joint fluid is a critical step in diagnosis.
    The finding of noninflammatory joint fluid in an acutely inflamed joint should prompt consideration of juxta-articular osseous pathology (eg, stress fracture, osteomyelitis, avascular necrosis), acute inflammation of periarticular structures (eg, gouty inflammation of tendon sheaths or bursae, septic bursitis), subcutaneous inflammation (eg, arthritis of ankles in erythema nodosum, pancreatic fat necrosis), or cellulitis.
    Initial treatment of possible septic arthritis6,29
  • Begin intravenous antibiotic therapy if the possibility of septic arthritis cannot be excluded with reasonable certainty after the initial clinical and laboratory evaluation.
    Provide for adequate drainage of the joint. Repeated percutaneous aspiration of the joint with a large-bore needle is indicated. Arthroscopic drainage of knees, shoulders, ankles, and elbows is an acceptable alternative, provided the risk of anesthesia is not excessive. Use surgical drainage for hips and for other joints that cannot be adequately drained with needle aspiration or that do not improve after 3-5 days of repeated percutaneous aspiration. Initial treatment of acute crystalline synovitis4
  • NSAIDs should initially be given at their maximum recommended dosage until symptoms improve. Then, they should be tapered gradually over several days. Indomethacin is very effective, but adverse effects in some patients limit its utility. Other NSAIDs with short half-lives (eg, ibuprofen, diclofenac) can also be used.
    Colchicine has a narrow therapeutic window, which limits its effectiveness. It must be used cautiously in the setting of renal insufficiency. Thus, its use to treat acute gouty arthritis (as opposed to low doses to prevent attacks) has been largely supplanted by other therapies.
  • Corticosteroids are an effective alternative to NSAIDs and colchicine for patients in whom these drugs may be contraindicated or hazardous (eg, patients with advanced age, renal insufficiency, congestive heart failure, inability to take oral medications). Regimens include (1) an intramuscular injection of a long-acting crystalline preparation (eg, triamcinolone acetonide at 60-80 mg), with an option to repeat once after 24-48 hours; (2) prednisone at 20-30 mg/d with a progressive taper over 7-10 days; and (3) intra-articular corticosteroid therapy.
  • Acute polyarthritis30
    Principles of management
    Hospitalize the patient in the presence of (1) significant, concomitant internal organ involvement; (2) signs of bacteremia, including vesiculopustular skin lesions, Roth spots, shaking chills, or splinter hemorrhages; (3) systemic vasculitis; (4) severe pain; (5) severe constitutional symptoms; (6) purulent (group III) synovial fluid in one or more joints; or (7) immunosuppression.
  • An infectious etiology should receive first consideration. Obtain appropriate cultures (eg, blood, joint, cervix, urethra, pharynx). Begin empiric antibiotic therapy if bacteremia or sepsis cannot be readily excluded.
  • Extra-articular manifestations, such as a rash, hematologic abnormalities, or heart murmur, should be sought as important indicators of the diagnosis.
  • Repeated examinations of the patient are required to detect diagnostic physical findings that may be absent at presentation.
  • Initial treatment modalities for patients with acute polyarthritis
    Antibiotic therapy is indicated for septic polyarthritis or bacteremia with joint involvement (eg, disseminated gonococcemia). Systemic antibiotics are used after appropriate cultures are taken. Prolonged treatment of reactive arthritis with antibiotics is not supported by current evidence.31
  • Analgesics without anti-inflammatory properties may be appropriate as the initial treatment in patients with milder forms of acute rheumatic fever, viral arthritis (eg, parvovirus arthritis), or acute leukocytoclastic vasculitis. They also may be appropriate for those with polyarticular crystalline synovitis in whom significant concomitant medical problems preclude the use of NSAID or corticosteroid therapy. This therapy allows for the complete expression of the clinical manifestations of the disease, thereby aiding in diagnosis.
  • High-dose aspirin therapy can be used for acute rheumatic fever, with the goal of achieving a salicylate level of 20-30 mg/dL. High-dose NSAID (nonsalicylate) therapy is used to treat crystalline synovitis, acute viral arthritis, and polyarthritis related to rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or other connective-tissue disorders.
    Corticosteroids are used in persons with polyarthritis alone in whom high-dose NSAID therapy has failed or who cannot be treated safely with NSAIDs because of renal insufficiency, active GI bleeding, or other conditions. Prednisone at 15-20 mg/d (or equivalent) is usually sufficient for acute polyarticular flares of RA. High doses of prednisone (0.5-1 mg/kg/d) are used in the setting of severe constitutional symptoms, concomitant major organ involvement, or signs of systemic vasculitis. Examples include acute SLE, Still disease, or acute rheumatic fever that fails to respond to NSAID therapy.
  • Chronic (inflammatory) monoarthritis
  • Principles of management
    Diagnoses other than osteoarthritis should be considered if the patient has a synovial fluid WBC count of greater than 1000/µL, hemorrhagic synovial fluid, no significant radiographic changes associated with osteoarthritis, synovial proliferation, significant pain, or constitutional symptoms.
  • The initial diagnostic focus in a patient with a chronic inflammatory monoarthritis is always on a potential infectious etiology. (Lyme arthritis can manifest as a subacute or chronic inflammatory monoarthritis; its diagnosis is based on the results of serologic testing. Antibiotic treatment is indicated.)
  • Perform a synovial biopsy and culture if the initial evaluation (including synovial fluid cultures) fails to establish a specific diagnosis.
    Consider aseptic necrosis in a joint with noninflammatory joint fluid.
    Treatment modalities for patients with chronic (inflammatory) monoarthritis
    Chronic gout therapy requires allopurinol (the preferred drug) to correct hyperuricemia. Suppress chronic inflammation with NSAIDs, colchicine (eg, 0.6 mg bid), or both. Intra-articular corticosteroid therapy may also be appropriate.
    Other crystalline arthropathies (calcium pyrophosphate, hydroxyapatite) are treated by suppressing chronic inflammation with NSAIDs, colchicine, or both. Intra-articular corticosteroid therapy may also be appropriate.
    Monoarticular presentation of a systemic rheumatic disease is treated with systemic therapies appropriate to the rheumatic disease, particularly if intra-articular corticosteroids are contraindicated or ineffective for long-term suppression of the monoarticular disease.
  • Chronic (inflammatory) polyarthritis
    Principles of management
    Treatment with NSAIDs is often initiated before a firm diagnosis is established.
    Certain diagnoses should be sought during the initial patient evaluation because specific (and potentially curative) therapies are needed. These include chronic polyarticular gout, subacute bacterial endocarditis, and hepatitis C–related syndromes (eg, cryoglobulinemia, arthritis).
  • Disease-modifying antirheumatic drugs (DMARDs) such as methotrexate, leflunomide, and tumor necrosis factor-alpha antagonists should be started relatively early in the course of rheumatoid or psoriatic arthritis in order to prevent joint damage. Consultation with a rheumatologist is prudent in order to confirm these diagnoses and to initiate appropriate DMARD therapy.
  • Corticosteroids in low doses (≤10 mg) may serve as a valuable adjunct to the treatment of chronic inflammatory arthritides, although attention must be paid to the adverse effects of long-term steroid use (eg, osteoporosis).
  • Treatment modalities
  • NSAID choice is guided by the patient's comorbidities and past response to these drugs. It is also guided by the cost and dosing frequency of the drugs. Maximal doses of NSAIDs are generally required for effective management of chronic polyarthritides. However, lower doses may be used if the disease is being adequately suppressed with DMARDs.
    DMARDs are used to suppress synovitis and thereby prevent or at least retard the development of joint damage and/or deformity. The choice of DMARD regimen depends on a number of factors, including the underlying disease, comorbidities, and prior treatment responses, among others. Guidelines for the use of DMARDs in various polyarthritides are presented in other eMedicine articles (eg, see Rheumatoid Arthritis).
  • Osteoarthritis
    Principles of management
    Management is most effective when it includes physical measures to reduce joint loading, an appropriate exercise regimen, medications, and, occasionally, surgery.
    The natural history of osteoarthritis is punctuated by episodes of more intense joint pain, followed by long periods of relative quiescence. More persistent, chronic pain is a feature of advanced disease. Dosing of anti-inflammatory and analgesic medications should be calibrated to the severity of the joint pain. Acute episodes may require enforced joint rest for relief; use of crutches, a cane, splints, or other orthotic devices; and strict avoidance of certain activities.
  • Prevention of symptomatic flares is key to proper management. Patients should be educated to maintain or achieve ideal body weight, exercise to strengthen muscles that support diseased joints, and avoid specific activities that aggravate joint pain (eg, stair climbing, strenuous exercise, throwing, kneeling).
  • Nonpharmacologic management
  • Instruct the patient to attempt to achieve and/or maintain ideal body weight.
    Teach the patient joint preservation techniques.
    Recommend a physical therapy regimen that includes range-of-motion and flexibility, conditioning, and aerobic cardiovascular exercises.
    Prescribe orthotic devices (eg, cane, walker, splint, wedged insoles) to rest or unload a joint.
    Recommend the use of devices to assist activities of daily living (eg, tub seat, elevated toilet, dressing sticks, long-handled shoe horns).
    Pharmacologic management32,33
    Mild disease can be treated with acetaminophen (up to 1 g qid); tramadol (50-100 mg qid); over-the-counter NSAIDs (eg, naproxen, ibuprofen) in analgesic doses; glucosamine (500 mg tid); or topical analgesics containing capsaicin, methylsalicylate, or an NSAID.
    Moderate disease is treated with NSAIDs. Persistent symptoms not relieved by mild therapy often require NSAID administration for prolonged periods in anti-inflammatory doses. In this setting, give careful consideration to potential NSAID toxicities. Avoid long-term use of indomethacin, piroxicam, and mefenamic acid. Use of the COX-2 inhibitor, celecoxib, is associated with a lower frequency of serious GI complications. Celecoxib is an option for patients with a history of peptic ulcer disease or previous upper GI bleeding and for those taking anticoagulants or oral corticosteroids. It should be avoided in patients with significant cardiovascular disease or risk factors. The risk of NSAID gastropathy can be reduced by coadministering a proton pump inhibitor.
  • Intra-articular hyaluronan may provide relief of symptomatic knee osteoarthritis for periods up to 1 year. It requires a series of 3-5 weekly injections. Intra-articular corticosteroids are beneficial for patients with symptomatic effusions. Use is limited to 1 injection per joint every 3 months.
    Severe disease is the presence of intractable pain and/or significant incapacity, and this is an indication for surgical intervention. Opiate analgesics may be used for intractable pain, but first thoroughly consider the risks associated with their long-term use.
    Soft tissue rheumatic pain disorder
    Principles of management of regional musculoskeletal pain syndromes (eg, tendonitis, bursitis, acute soft tissue injuries, and regional myofascial pain syndromes)11
    Allow the soft tissue injury to heal with a short period of enforced rest. This can be achieved with immobilization or avoidance of activities that require the use of the involved part.
  • Provide pain relief using both nonpharmacologic (eg, local heat or cold, electrical stimulation, massage) and pharmacologic (eg, oral analgesics, NSAIDs, muscle relaxants, corticosteroid injections, topical agents) modalities.
    Prescribe an exercise program to be performed at home or under the guidance of a physical therapist. The goals should include stretching, muscle strengthening, and education about proper body mechanics.
  • Identify and eliminate factors that have aggravated or precipitated soft tissue pain (eg, posture, repetitive trauma, poor body mechanics).
    Principles of management of generalized noninflammatory soft tissue rheumatic pain syndromes (eg, fibromyalgia, hypermobility syndrome)
    Screen for coexistent depression, and treat it if present.
    Screen for a sleep disorder, and treat it if present.
    Emphasize the primary role of low-level aerobic exercise in treatment.
    Treat pain using agents that are acceptable for prolonged use and do not promote physical dependence.

  • Surgical Care
    Indications for surgical management of arthritis include the following:

    Uncertain diagnosis: Perform a synovial or bone biopsy.
    Acute septic arthritis6
    Drain hip and shoulder joints.
    Surgically drain joints that are not responding to repeated percutaneous needle drainage.
    Remove hardware or exchange polyethylene components in an infected prosthesis.
  • Rheumatoid arthritis
    Perform total arthroplasty on large joints, such as hips, knees, and shoulders. The primary indication is relief of pain that has failed to improve with medical therapy. Improvement of function and motion are secondary goals that are not always attainable.
    Perform wrist synovectomy and dorsal hand tenosynovectomy for persistent synovitis of the dorsum of the wrist and hand that threatens tendon integrity.
    Correct atlantoaxial or subaxial subluxation in the cervical spine.
    Perform reconstructive surgery of the hands and feet.
  • Osteoarthritis
    Use arthroscopic surgery to correct internal derangements (eg, meniscal tears) and to remove loose bodies that are causing mechanical symptoms.
    Perform an osteotomy to distribute weight in the compartment of a joint with relatively preserved cartilage.
    Total arthroplasty is indicated to relieve the pain of advanced joint disease; improvement of function and motion are secondary goals.
    Joint fusion is indicated on joints such as the ankle (eg, triple arthrodesis) or carpometacarpal joints in order to relieve pain and instability.


    Patient Education

    For excellent patient education resources, visit eMedicine's Hand, Wrist, Elbow, and Shoulder Center. Also, see eMedicine's patient education article Tennis Elbow.

    Differential Diagnoses & Workup
    Treatment & Medication