16. | Manual of Rheumatology and Outpatient Orthopedic Disorders (LB Spiral Manuals)

Chapter 9 Monarthritis/Polyarthritis: Differential Diagnosis

Manual of Rheumatology and Outpatient Orthopedic Disorders

Chapter 9 Monarthritis/Polyarthritis: Differential Diagnosis

Stephen Ray Mitchell and John F. Beary, III

Acute monarthritis
Chronic monarthritis
Acute polyarthritis
Chronic polyarthritis

The number of joints and the time course during which a joint disorder develops guide the approach to differential diagnosis. Acute monarthritis may represent septic arthritis, which is a rheumatologic emergency. Prompt diagnosis and treatment of a potentially septic process are required. The single abnormal joint that persists beyond 2 months presents a different diagnostic challenge. In each case, one must view the overall clinical presentation, including factors such as associated extraarticular visceral involvement, constitutional signs and symptoms, severity of illness and limitation of function, potential foci of infection, skin lesions, hyperuricemia, and history of trauma or bleeding disorders. Usually, an aggressive initial approach is indicated, including joint aspiration with synovial fluid analysis and occasionally referral for synovial biopsy or arthroscopy. Therapy will vary significantly depending on the presumptive diagnosis. Specific therapy of each disease is discussed in later chapters. Table 9-1 and Table 9-2 summarize the diagnostic approach to this group of disorders.

Table 9-1. Differential diagnosis of monarthritis by presentation

Table 9-2. Differential diagnosis of polyarthritis by presentation

I. Acute monarthritis

Infectious arthritis generally develops with an abrupt onset and marked inflammatory response. Because prompt therapy is required to prevent joint damage or systemic sepsis, it is important to diagnose bacterial infection promptly.
One may be deceived, however, in a partially treated patient on oral antibiotics or in an immunosuppressed patient by the mild appearance of the joint. A prudent approach includes careful examination for associated infectious foci and clues (e.g., cutaneous pustules with neisserial infection), prompt joint aspiration, synovial fluid culture and Gram's stain , and empiric antibiotics (depending on age and epidemiology). A viral process is typically polyarticular (except transient synovitis of the hip in childhood, which is thought to be viral or postviral in origin). Lyme arthritis, caused by a Borrelia spirochete, can present acutely as recurring knee monarthritis, but more often it presents early in the course of the disease as migratory polyarthralgias (see Chapter 41).
Crystal-induced disease
1. Gout classically presents as podagra with abrupt, intense onset of pain in the first metatarsophalangeal joint; it often affects the midfoot and ankle but can involve any joint or bursa. Typically, a man in his thirties or a postmenopausal woman (often using thiazide diuretics, which cause hyperuricemia) presents with monarthritis of the lower extremity . However, 30% present with polyarticular synovitis. Between episodes , the joints return to normal unless chronic disease develops. Check carefully for tophi on the ears, elbows, or feet. At a younger age of onset, one must think of lymphoma or other disorders associated with rapid cell turnover . Joint aspiration is diagnostic for negatively birefringent, needle-shaped crystals within white blood cells . Note that gout can coexist with pseudogout, and both can coexist with infection (see Chapter 37).
2. Calcium pyrophosphate dihydrate (CPPD) deposition disease (pseudogout) is an acute or subacute process in the elderly with involvement of large or small joints (including the second and third metacarpophalangeal joints).
  Chondrocalcinosis can often be defined radiographically in the knee, symphysis pubis, or triangular cartilage of the wrist. Crystals found within white blood cells are rhomboid-shaped and positively birefringent. In those patients who present at a younger age, other diagnostically important, treatable medical conditions, such as hemochromatosis, hyperparathyroidism, or Wilson's disease, must be considered (see Chapter 38).
Hemarthrosis is defined as the aspiration of bloody joint fluid.
1. Trauma usually is associated with a relevant history of injury . A layer of fat (from the bone marrow) seen on top of bloody fluid implies intraarticular fracture even in the presence of negative radiographs.
2. Internal derangement. Meniscal tears involving avascular portions of knee fibrocartilage may not be bloody but can cause intermittent locking, giving way, and a positive Macmurray maneuver (a painful click produced by extending the knee when the foot is internally or externally rotated ). Instability of the collateral and cruciate ligaments is also a clue to this condition (see Chapter 22).
3. Nontraumatic hemarthrosis may be seen with anticoagulation, after dialysis, or with benign neoplasms such as pigmented villonodular synovitis, synovial osteochondromatosis, or hemangioma of the synovium. Diagnosis is confirmed with synovial biopsy, arthroscopy, or magnetic resonance imaging (MRI).
Periarticular syndromes. Any of the tissues surrounding the joint can be involved in an inflammatory or traumatic process. A careful musculoskeletal examination can distinguish between tendinitis, bursitis, overuse syndromes, and surrounding cellulitis. Erythema nodosum is often seen with drug reaction, inflammatory bowel disease, or acute sarcoidosis. It often causes a periarthritis about the ankles and can result in an associated joint effusion. Osteomyelitis or neoplasia should be considered with focal bone pain. Severe periarticular pain in a child, nocturnal in nature, is uncommon with juvenile arthritis and should always suggest leukemia.
Noninfectious inflammatory conditions
1. Seronegative spondyloarthropathies. Because of the highly inflammatory, monarticular nature of some episodes of joint inflammation associated with Reiter's syndrome or psoriatic arthritis, the clinical presentation may be indistinguishable from that of infection. The diagnosis may be supported by the presence of characteristic extraarticular features, such as a psoriasiform rash, eye inflammation , or urethritis. A history of low back symptoms or tenderness over the sacroiliac joints suggests the diagnosis of spondyloarthritis and is an indication for radiographic study of the sacroiliac joints (see Chapter 33).
2. Juvenile rheumatoid arthritis (JRA). The child who presents with monarthritis and a negative infection workup may well have pauciarticular (fewer than four joints) JRA (see section II.B.3 and Chapter 25). Transient synovitis of the hip characteristically presents as a monarthritis of the hip in a child following a viral illness. The child is nontoxic in appearance and has a culture-negative joint effusion. This self-limited disorder is felt to be mediated by a virus or immune complexes and responds to bed rest and antiinflammatory medications.
Monarticular presentation of a polyarticular disease. Although rheumatoid arthritis (RA) characteristically evolves into a symmetric polyarthritis, some patients present, at the onset of the disorder, with a monarticular synovitis. Attacks of palindromic rheumatism resemble gout. These are intense inflammatory episodes that involve a single joint and periarticular tissues. They last days at a time, with a return to normal between episodes. Later, the more typical, polyarticular pattern of RA emerges (see Chapter 28).

II. Chronic monarthritis. A single involved joint that persists beyond 2 months represents a somewhat different group of diseases. Some conditions will resolve; others will progress to a polyarticular presentation. The finding of other involved joints alters the diagnosis significantly, in that the presence of oligoarthritis makes infection and neoplasia much less likely.

Infectious conditions
1. Pyogenic bacterial infections. Most untreated pyogenic bacterial infections present in an acute fashion because of their virulence. These processes rarely persist in a chronic fashion unless they are partially treated.
2. Bacterial osteomyelitis. There is the rare occurrence of an associated bacterial osteomyelitis or an organism that is a low-virulence bacterial pathogen.
3. Fungal infection in an immunocompromised host, or following penetration of a splinter or plant thorn, may develop subacutely and persist in a single joint.
4. Lyme arthritis commonly persists for months to years after the primary infection as a recurring, inflammatory monarthritis, most commonly in the knee. In children in endemic areas, it is equally as common for the child to have Lyme disease as to have JRA.
5. Tuberculous arthritis usually presents subacutely as an inflammatory process in a single joint. Often, but not always, there is evidence of prior mycobacterial disease in the lung, and the patient demonstrates a positive skin test reaction to tuberculin. In contrast to a bacterial process, tuberculous arthritis may arise from a subchondral focus of osteomyelitis and often leads to bony erosions with the absence of joint space narrowing.
Noninfectious inflammatory disorders
1. Seronegative spondyloarthropathies may be the most common causes of chronic inflammatory monarthritis. Important clinical clues include the presence of low-back or buttock pains with morning stiffness reflecting spinal involvement or inflammation of the sacroiliac joints; extraarticular features, such as pitting of the nails or a scaling skin rash (psoriasis); characteristic skin lesions, such as keratoderma blennorrhagicum or circinate balanitis, associated with urethritis and conjunctivitis (Reiter's disease); a history consistent with inflammatory bowel disease (ulcerative colitis or Crohn's disease); or a history of uveitis.
2. Rheumatoid arthritis can present as chronic monarthritis and requires additional months of observation before the typical symmetric joint distribution develops.
3. Pauciarticular JRA is often monarticular. The joint involvement may be much less impressive than the potentially devastating, asymptomatic chronic iridocyclitis that can occur in patients with antinuclear antibodies.
4. Sarcoid arthropathy can be associated with monarthritis, and associated erythema nodosum and hilar adenopathy will often suggest the diagnosis. More typically, there will be oligoarthritic involvement, with a prominent periarthritis about the ankles.
Noninflammatory conditions
1. Osteoarthritis is called osteoarthrosis in Europe to emphasize the noninflammatory nature of the disease. Osteoarthritis usually is of an insidious onset in the hands and weight- bearing joints. It is less common, in the absence of trauma, in the wrist, ankle, elbow , or shoulder. Patients present with pain or brief morning stiffness in one or more hand joints or in a single weight-bearing joint. Symptoms may occur at the end of the day or following activity. Studies reveal normal laboratory data, a noninflammatory joint fluid, and a radiograph that may show asymmetric joint space narrowing, subchondral sclerosis, or osteophyte (spur) formation. The presence of chondrocalcinosis on radiographs may account for symptoms in joints uncommonly involved in osteoarthritis, such as the wrist or second or third metacarpophalangeal joints.
2. Internal derangement of the knee (see section I.C.2 ). If untreated, this problem can lead to recurrent effusion, pain, and premature osteoarthritis.
3. Avascular necrosis of bone. Avascular necrosis of bone (also called osteonecrosis ) is associated with monarticular pain and decreased range of motion in hips, knees, or shoulders resulting from ischemic necrosis of bone and the underlying bone marrow. While half of patients have no obvious cause, this condition is associated with steroid use, systemic lupus erythematosus (with or without a history of corticosteroid therapy), alcoholism, hemoglobinopathies, and Gaucher's disease.
  Avascular necrosis of bone may involve multiple sites, and some of them remain asymptomatic and are defined only radiologically. Typical radiographic changes are subchondral crescent-shaped, lucent areas (the crescent sign) within the femoral head. This may be followed by bone remodeling and collapse if weight bearing is not interrupted . In the chronic phase, secondary degenerative changes may occur. If the findings on plain films are normal, an early diagnosis can be made by a nuclear bone scan or MRI (see Chapter 45).
4. Neoplasia. As noted above, the most common benign joint neoplasms are synovial chondromatosis and pigmented villonodular synovitis. The best preoperative diagnostic test is an MRI study, which will reveal radiolucent cartilaginous or synovial lesions.

III. Acute polyarthritis. The involvement of two to four joints (oligoarthritis) or more than four joints (polyarthritis) raises the possibility of several diseases listed in Table 9-2. The pattern in which the arthritis develops is often diagnostically helpful.

Infectious conditions. When an acutely painful, warm, swollen joint develops then returns to normal while synovitis occurs in another joint, the patient is categorized as having migratory polyarthritis. This group of disorders includes important, treatable diseases for which prompt diagnosis is crucial.
1. Bacterial infection. The young adult with migratory polyarthritis, often associated with tenosynovitis and cutaneous pustular lesions, may have a disseminated bacterial process such as disseminated neisserial infection. Most commonly seen with Neisseria gonorrhoeae, the same syndrome can occur with Neisseria meningitidis. Both require prompt treatment with parenteral antibiotics. Most pyogenic bacteria produce a monarthritis, as does the late presentation of gonococcal arthritis. Polyarticular bacterial arthritis is unusual except in the immunocompromised host (see Chapter 40).
2. Reactive (or postinfectious) arthritis
  1. Acute rheumatic fever should be strongly considered in the young patient with migratory polyarthritis. A search for serologic evidence of a recent streptococcal infection with a rising antistreptolysin O (ASO) titer will support this diagnosis. Although the Jones criteria are helpful in making the diagnosis, acute rheumatic fever may occur in the absence of carditis, rash, or chorea. The arthritis associated with acute rheumatic fever typically is exquisitely painful, sometimes out of proportion to any effusion or synovitis, and is usually abrupt in onset (see Chapter 43).
  2. Reiter's syndrome can also cause an acute, reactive polyarthritis following dysentery or urethral infection. The arthritis is often more explosive and usually more sustained than in acute rheumatic fever. Patients may or may not demonstrate the characteristic Reiter's triad of arthritis, urethritis, and conjunctivitis.
3. Spirochetal infection. Borrelia burgdorferi infection during the primary, early stage of Lyme disease can lead to a migratory polyarthralgias associated with low-grade fever and symptoms typical of viral infection. Late Lyme disease assumes a more oligoarthritic pattern that waxes and wanes. The diagnosis is supported by the clinical presentation, the presence of an erythema chronicum migrans rash, and serologic testing.
4. Viral infection. Classically, viral arthritis is polyarticular and may, at times, be migratory. The prodromal, preicteric phase of hepatitis B can present classically with rash and arthritis. Other viruses known to produce a polyarticular presentation are rubella virus (including after vaccination), mumps virus, Epstein-Barr virus (infectious mononucleosis), and parvovirus B19. Parvovirus causes fifth disease or erythema infectiosum, a febrile exanthem in children. It can mimic acute rheumatic fever with a migratory polyarthritis or can produce an RA-like, seronegative chronic polyarthritis in adults and some children.
5. Miscellaneous infections. Infections with Rickettsia, fungi, or parasites can lead to polyarticular disease but are less common.
Noninfectious inflammatory conditions
1. Rheumatoid arthritis. Although usually insidious in onset, RA can present with an acute polyarthritis. Early on, these patients may be seronegative for rheumatoid factor but may have fatigue, anemia, and thrombocytosis. Fever is not commonly seen in RA.
2. Polyarticular JRA may present differently in subsets of children.
  1. The younger child has a seronegative oligoarthritis that is often insidious in onset. Serum in approximately 25% will be positive for antinuclear antibodies. A potentially destructive iridocyclitis is seen in this group of children.
  2. Another group of children may present with systemic-onset JRA, with high spiking fevers, a transient rash, hepatosplenomegaly, lymphadenopathy, and polyarticular or oligoarticular joint complaints that develop later.
  3. The preadolescent girl, in contrast, may present with rheumatoid factor positivity, nodules, and an erosive polyarticular joint disease similar to adult RA (see Chapter 25).
3. Systemic lupus erythematosus (SLE) is a classic immune complex disorder that characteristically presents with an RA-like polyarthritis of the small joints of the hands and feet. Marked proliferative synovitis speaks against the diagnosis of SLE. Erosive disease is rare, but the presence of reversible deformity is not. Other clinical features, such as serositis, fever, skin rash, and renal disease, may provide clues to the diagnosis. Laboratory abnormalities can include the presence of serum antinuclear antibodies, anemia, and thrombocytopenia (see Chapter 30).
4. Other connective tissue diseases include a spectrum of disorders that produce inflammatory disease of muscles , soft tissues, small blood vessels, and viscera. The initial presentation may include polyarthritis, but more diagnostic features evolve , including Raynaud's phenomenon with digital infarcts, skin thickening, dysphagia, and pulmonary fibrosis suggestive of scleroderma; proximal myopathy and skin rash characteristic of polymyositis/dermatomyositis; and overlap features seen in mixed connective tissue disease.
5. Seronegative spondyloarthropathies. This group of diseases is characterized by presence of the class I histocompatibility antigen HLA-B27; axial arthritis, including spondylitis and sacroiliitis; and inflammatory disease of the eye, skin, and ligamentous insertions (enthesopathy). The joint pattern is usually oligoarthritic and asymmetric, and large joints of the lower extremity are involved. Rheumatoid factor and antinuclear antibodies are not usually found in the serum of these patients. The specific diagnosis is usually defined by the associated clinical features: psoriatic arthritis by the presence of psoriasis, Reiter's syndrome by the concomitant conjunctivitis and urethritis, and enteropathic arthritis by the presence of ulcerative colitis or Crohn's disease.
  1. Ankylosing spondylitis has perhaps the least association with peripheral joint involvement of the group; it usually presents insidiously with symptoms in the axial spine. However, inflammatory involvement of the peripheral joints may develop in 25% to 30% of patients at some point in the disease. This most often involves the hips and shoulders (see Chapter 33).
  2. Reiter's syndrome typically has a markedly acute presentation of polyarthritis. The triad of conjunctivitis, urethritis, and asymmetric oligoarthritis may not always occur simultaneously , and limited disease has been recognized. Disease onset often follows dysentery or urethritis caused by a number of pathogens. Enthesopathy (inflammation of ligamentous or tendon insertions) and joint inflammation cause the classic sausage digit or dactylitis that enlarges the joints and soft tissues of the toes or fingers.
    Extraarticular features that are most helpful in diagnosis include circinate balanitis (a psoriasiform rash encircling the glans penis) or a hyperkeratotic rash on the feet (keratoderma blennorrhagicum) (see Chapter 36).
  3. Psoriatic arthritis can present as asymmetric oligoarticular arthritis of large and small joints; it can also present as a symmetric polyarthritis indistinguishable from RA. Dactylitis, psoriasis, and nail dystrophy are clinical features used to distinguish psoriatic arthritis from RA. Nail involvement, often simple pitting, may be present in 60% of patients with arthritis and psoriasis and is found in only 5% of those with psoriasis alone (see Chapter 35).
  4. Enteropathic arthritis usually presents as an asymmetric polyarthritis of the lower extremities, which can predate known inflammatory bowel disease by months to years. It is typically nonerosive, and the peripheral joint inflammation usually responds to therapy of the underlying bowel disease. The axial arthritis may not respond as well. Clues to the diagnosis include abdominal pain, abnormal bowel movements, erythema nodosum, or pyoderma gangrenosum associated with a spondylitic presentation (see Chapter 34).
6. Crystal-induced disease
  1. Gout can present as polyarticular disease in the setting of long-established tophi. In men, there generally will be a history of previous, typical, acute oligoarticular attacks; however, in postmenopausal women on thiazides, there is a well-described presentation of diffuse tophaceous, polyarticular disease without previous episodic disease. Virtually every joint can be involved, and significant fever and leukocytosis can be present. Diagnostic clues include palpable tophi in the olecranon bursa or along the pinna of the ear and characteristic erosions on radiographs of the hands or feet. Characteristic negatively birefringent crystals in the synovial fluid white blood cells and polyarticular or tophaceous disease make a septic process much less likely, but gout and joint sepsis can coexist. Similarly, gout and pseudogout crystals can be found in the same inflamed joint (see Chapter 37).
  2. Calcium pyrophosphate dihydrate deposition disease. The presentations of CPPD deposition disease include (a) acute monarticular pseudogout, (b) atypical osteoarthritis, (c) Charcot-like knee disease, and (d) polyarticular disease in the hands and wrists that can mimic RA. Clues include radiographic evidence of chondrocalcinosis of the triangular cartilage of the wrist, the symphysis pubis, or the knees and the identification of typical, weakly positively birefringent rhomboid crystals in synovial fluid white blood cells. As previously discussed, it is important to exclude associated treatable medical illnesses such as hyperparathyroidism and hemochromatosis (see Chapter 38).
7. Serum sickness presents as an acute, sometimes migratory polyarthritis that develops 10 to 14 days after antigen exposure stimulates the formation of immune complexes. The antigen can be antibiotics or other drugs, or biologics such as horse or human antisera. The clinical response is fever, poly-arthritis, pruritus, and a rash. The rash is often urticarial and sometimes petechial. Adenopathy and occasionally renal disease may occur. Laboratory assessment reveals mild leukocytosis, normal or mild elevation of the sedimentation rate, rare eosinophilia, and decreased serum complement. The heterophil reaction may be positive, and circulating immune complexes can be detected .
8. Sarcoidosis presents as a periarthritis or polyarthritis associated with hilar adenopathy, erythema nodosum, and fever (Lfgren syndrome). A similar disorder can occur without adenopathy and can be due to infections (streptococci, TB, coccy), inflammatory bowel disease, and drug reactions .
9. Vasculitis
  1. Small-vessel involvement. Polyarthritis may be seen in types of vasculitis in which small vessels are inflamed. This includes the leukocytoclastic angiitis Henoch-Schnlein purpura. Typically, dependent and at times confluent areas of nonthrombocytopenic purpura are present from the feet to the waistline in association with inflammatory arthritis of the ankles and knees.
  2. Medium- sized vessel involvement. An inflammatory arthritis may also be present when medium-sized vessel involvement leads to systemic necrotizing vasculitides, such as Wegener's granulomatosis or polyarteritis nodosa.
  3. In children, Kawasaki disease is characterized by a febrile exanthem associated with adenopathy, mucositis, ocular changes, and devastating coronary arteritis. This disorder, thought to be the most common vasculitis of childhood, causes an inflammatory polyarthritis in one-third of patients (see Chapter 25).
10. Hematologic disorders. Polyarthritis may be the presenting or an early manifestation of leukemia, lymphoma, or sickle cell disease. Diagnostic clues are periarticular pain, bone pain, and nocturnal pain, as well as an associated known hematologic disorder. In children who present with these symptoms, a bone marrow aspirate is indicated, even in the presence of a normal peripheral blood smear.

IV. Chronic polyarthritis involves four or more joints and persists longer than 2 months. Oligoarthritis involves fewer than four joints, often in an asymmetric fashion.

Rheumatoid arthritis. The arthritis is usually an additive (joints do not return to normal between episodes), symmetric polyarthritis of the small joints of the hands and feet. Larger joints of the upper and lower extremities and neck are also commonly involved. Rheumatoid factor may not be present in the serum early in the disease. However, eventually 80% of patients are positive for rheumatoid factor. Extraarticular manifestations include constitutional features such as weight loss and fatigue, subcutaneous nodules, and anemia (see Chapter 28).
Systemic lupus erythematosus. Nearly 70% of patients will present with joint complaints. The arthropathy is usually an RA-like polyarthritis that is nonerosive. The diagnosis of SLE is based on the multisystem clinical presentation and is supported by the finding of serum antinuclear antibodies.
Other connective tissue diseases and overlap syndromes
1. Scleroderma (progressive systemic sclerosis) often produces arthralgias and morning stiffness, but signs of joint inflammation are uncommon. The diagnosis of scleroderma is based on a history of Raynaud's phenomenon, multisystem illness involving the lungs, kidneys, and gastrointestinal tract , and characteristic skin findings.
2. Polymyositis. Arthralgias may be reported in about one-third of patients with polymyositis, but joint problems are not a major aspect of this disease.
3. Overlap syndrome is a term that recognizes that connective tissue diseases such as RA, SLE, scleroderma, and polymyositis have overlapping clinical and serologic features.
Seronegative spondyloarthropathies (see section III.B.5 ). In patients with psoriatic arthritis, Reiter's syndrome, or ankylosing spondylitis, a chronic phase may develop. Characteristic features include sacroiliitis, asymmetric oligoarthritis or polyarthritis of the lower extremities, and spondylitis. Even Reiter's disease, with its typical episodic flares of activity, becomes chronic in nearly 75% of patients.
Crystalline disease (see section III.B.6 ). As acute gouty attacks become more frequent, the joints may no longer return to normal. Patients begin to experience constant symptoms, including morning stiffness. Radiographs of patients with untreated chronic tophaceous gout can sometimes demonstrate joint changes similar to those of RA; such abnormalities may also be seen with the symmetric, polyarticular variant of CPPD deposition disease.
Osteoarthritis. Despite the lack of systemic features, osteoarthritis in some people can be diffuse in distribution, mildly inflammatory, and associated with significant, if slowly progressive, deformity and disability. The joint distribution typically involves the first carpometacarpal joint of the thumb; first metatarsophalangeal joint; distal and proximal interphalangeal joints of the hands, hips, and knees; and the cervical and lumbar spine (see Chapter 44).

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Copyright 2000 by Lippincott Williams & Wilkins
Stephen A. Paget, M.D., Allan Gibofsky, M.D., J.D. and John F. Beary, III, M.D.
Manual of Rheumatology and Outpatient Orthopedic Disorders

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