DDx: Rheumatoid Arthritis Flashcards Preview

11 RHEUMATOLOGY > DDx: Rheumatoid Arthritis > Flashcards

Flashcards in DDx: Rheumatoid Arthritis Deck (22):

Differential Diagnosis of Rheumatoid Arthritis:

Antinuclear antibodies (ANA): nonspecific finding in SLE, Sjogren and scleroderma.  Antinuclear antibodies characteristically occur in IgM form in patients with RA, but they are found less frequently than rheumatoid factors.

Anti-U1-ribonucleoprotein (RNP) antibodies are found in patients with mixed connective tissue disease, which is characterized by features of systemic sclerosis, polymyositis, and SLE.

Anti-Ro/SSA and anti-La/SSB antibodies are present in 10% to 60% of patients with SLE; however, these antibodies are less specific than anti-dsDNA antibodies because they can also be present in patients with rheumatoid arthritis, systemic sclerosis, and Sjögren syndrome.

Rheumatoid Arthritis

Ankylosing spondylitis 

CPPD deposition disease


Infective endocarditis 

Lyme disease


Psoriatic arthritis

Peripheral arthritis associated with IBD

Reactive arthritis

Infectious arthritis

Systemic lupus erythematosus

Viral arthritis

Trochanteric bursitis

Anserine bursitis

Patellofemoral pain syndrome

Enteropathic Arthritis


Rheumatoid Arthritis

Rheumatoid arthritis is a symmetric polyarthritis that involves the small joints of the hands and feet as well as other joints throughout the body.

Hx: Usually is a symmetric polyarthritis affecting large and small joints; it rarely presents as monoarthritis. Soft tissue (synovial) swelling rather than bony enlargement of the PIP and MCP joints.  RA can affect most joints; however, the lumbar spine, thoracic spine. and distal interphalangeal joints are spared.  Flares may be monoarticular and present as pseudoinfectious arthritis.

Inflammatory signs (fatigue, prolonged morning stiffness), rheumatoid nodules, and inflammatory synovial fluid.

Morning stiffness lasting more than 60 minutes

Acute rheumatoid arthritis sometimes mimics gout. The greater the number of joints involved, the more likely that rheumatoid arthritis is the diagnosis.

Dx: Rheumatoid factor is positive in 80% of cases. Synovial fluid analysis including Gram stain and culture usually will distinguish a flare from infectious arthritis.

CRX: Bony erosions; periarticular osteopenia; subluxations; soft-tissue swelling; MCP and PIP involvement on hand radiograph

synovial fluid leukocyte count greater than 5000/µL (5 × 109/L).


DMARDs: Experts recommend that patients begin disease-modifying antirheumatic drugs (DMARDs) within 3 months of the onset of rheumatoid arthritis.

Methotrexate (Folic acid antimetabolite)

DMARD that is most likely to provide durable long-term response; often the initial choice

Takes 1-2 mo for full effect; frequently used in combination with other medications. Contraindicated in pregnancy and use with caution in patients who may become pregnant, have underlying liver or lung disease, immunosuppression, or infection. Folic acid supplementation prevents toxicity without interfering with efficacy.

Hydroxychloroquine (Antimalarial agent with lysosomotropic action that affects immune regulation and inflammation)

Early, mild, and nonerosive disease; in combination with methotrexate or when methotrexate is contraindicated

Takes 2-6 mo for full effect; frequently used in combination regimens. Use with caution in patients who are pregnant or who have antimalarial allergy, G6PD deficiency, or retinal disease. Perform annual ophthalmologic examination.

Sulfasalazine (Unknown mechanism)

Early, mild, and nonerosive disease; in combination with methotrexate or when methotrexate is contraindicated

Takes 1-2 mo for full benefit. Use with caution in patients with sulfonamide or aspirin allergy, G6PD deficiency, kidney or liver disease, blood disease, or asthma.

Leflunomide (Pyrimidine synthesis inhibitor)

In combination with methotrexate or when methotrexate is contraindicated for progressive disease

Contraindicated in pregnancy; use with caution in patients who may become pregnant (known teratogen) or have liver disease.

Biologic Agents:

TNF inhibitors (adalimumab, etanercept, certolizumab pegol, golimumab, infliximab)(Immunomodulation)

When adequate disease control is not achieved with one or more oral DMARDs, biologic therapy is indicated. The preferred initial biologic agent is a tumor necrosis factor α (TNF-α) inhibitor such as etanercept, which is usually added to baseline methotrexate therapy. Use of a TNF-α inhibitor in addition to methotrexate is significantly more effective in controlling joint damage and improving function compared with single-agent therapy with either medication alone.

Testing for latent tuberculosis required before starting therapy.

Interleukin-1 receptor antagonist (anakinra) (Immunomodulation)

Uncontrolled disease despite use of DMARDs

Testing for latent tuberculosis required before starting therapy.

T-cell costimulatory blocker (abatacept)(Immunomodulation) (down-regulation of T cells)

Uncontrolled disease despite use of DMARDs

Testing for latent tuberculosis required before starting therapy.

B-cell depleting agent (rituximab)(Monoclonal antibody against CD20)

Uncontrolled disease despite use of DMARDs

Testing for latent tuberculosis required before starting therapy.

Anti-inflammatory Agents

NSAIDs (Inhibit cyclooxygenase)

Mild disease without erosions; as an adjunctive analgesic in more serious disease

NSAIDs do not prevent disease progression. Use with caution in patients with chronic kidney disease or ulcer disease.

Glucocorticoids (Suppress inflammation at multiple points along the inflammatory cascade)

Low-dose or intra-articular injections when NSAIDs do not control symptoms and when DMARDs have not yet produced an effect

High-dose glucocorticoids are useful in treating serious extra-articular manifestations (eg, vasculitis).


Ankylosing spondylitis 

Inflammatory disorder of the axial skeleton; may have peripheral involvement; apical pulmonary fibrosis; back pain.

Hx: Onset of ankylosing spondylitis usually occurs in the teenage years or 20s and manifests as persistent pain and morning stiffness involving the low back that is alleviated with activity. This condition also may be associated with tenderness of the pelvis.

Differs from rheumatoid arthritis because ankylosing spondylitis uncommonly has peripheral involvement and usually involves the lumbar spine.

Dx: MRI of the sacroiliac joints is most likely to establish the diagnosis.

CRx: Sacroiliitis; squaring of the vertebral bodies; bridging vertical enthesophytes


Calcium pyrophosphate dihydrate (CPPD) deposition disease [Pseudogout]

Deposition of CPPD crystals in and around joints, most commonly the wrist, MCP joints, shoulder, and knee.

May be asymptomatic or have a varied presentation resembling rheumatoid arthritis, osteoarthritis, or gout-like inflammation. Cartilage calcification termed chondrocalcinosis, especially in the knee, symphysis pubis, shoulder, hip, and triangular cartilage of wrist, are pathognomonic.

Hx: No history of trauma; May be monoarticular or acute oligoarticular, with hot and red joints; may be chronic polyarticular in 5% of cases.

Osteoarthritis in unusual places (wrist, elbow, metacarpophalangeal joints, shoulder) without a history of trauma suggests CPPD deposition.

Px: Osteoarthritis in unusual places (wrist, elbow, metacarpophalangeal joints, shoulder)

Dx: Defined by finding CPPD crystals in synovial fluid and by chondrocalcinosis on radiographs.

Polarized microscopy reveals weakly positive birefringent crystals in synovial fluid. Radiographs show chondrocalcinosis.

Cartilage calcification termed chondrocalcinosis, especially in the knee, symphysis pubis, shoulder, hip, and triangular cartilage of wrist, are pathognomonic.



Gout (Crystal-induced synovitis) 

Deposition of monosodium urate crystals in and around joints. Initial attack is monoarticular, most commonly in the first metatarsophalangeal (MTP) joint. Chronic form may have symmetric involvement of small joints of the hands and feet, with tophi. Gout can have a pseudo–rheumatoid arthritis pattern. Polarized microscopy reveals strongly negative birefringent crystals in synovial fluid or tophi. Gout is highly uncommon in premenopausal women with normal kidney function.


Infective endocarditis 

Characterized by involvement of large proximal joints, fever with leukocytosis, and heart murmur. Obtain blood cultures in all patients with fever and polyarthritis. RF is a common finding in patients with endocarditis.


Lyme disease

Multisystem inflammatory disease caused by Borrelia burgdorferi. Early disease: erythema migrans rash and cardiac abnormalities. Late disease: intermittent monoarthritis or oligoarthritis that may become chronic. Rash and tick exposure or travel to an endemic area are important for the diagnosis. Obtain ELISA test; confirm a positive result with Western blot.

Doxycycline is the treatment of choice in patients who are not pregnant and >8 years old.  IV

Cefriaxone is reserved for early disseminated and late disease as oral doxycycline is very effective in resolving EM.



Degeneration of articular cartilage, most often affecting the DIP, PIP, first CMC, first MTP, hip, and knee joints and the cervical and lumbar spine.

Hx: Common sites of osteoarthritis in the hand include the first carpometacarpal joint (base of the thumb), as well as the distal and proximal interphalangeal joints. Involvement of the carpometacarpal joint leads to “squaring” of the contour of the joint.

Pain occurs with use; minimal soft-tissue swelling and morning stiffness.

Characterized by joint-space narrowing with associated bony enlargement (osteophytes) with no acute signs of inflammation. Patients may have acute exacerbation of joint symptoms, especially after use.

According to the American College of Rheumatology's clinical criteria, osteoarthritis of the knee can be diagnosed if knee pain is accompanied by at least three of the following features: age greater than 50 years, morning stiffness lasting less than 30 minutes, crepitus, bone tenderness, bone enlargement, and no palpable warmth. 

Morning joint stiffness that persists for less than 30 minutes

Px: Passive range of motion of the knee often elicits pain at the extremes of flexion and extension. 

Dx: Diagnosed (clinically) if knee pain is accompanied by at least three of the following features: age greater than 50 years, stiffness lasting less than 30 minutes, crepitus, bone tenderness, bone enlargement, and no palpable warmth. 

CRX: Asymmetric joint-space narrowing; osteophytes; subchondral sclerosis and cystic changes; degenerative disk disease with collapse of disks; degenerative joint disease with facet joint osteophytes; these findings lead to spondylolisthesis (anterior/posterior misalignment of the spine) and kyphosis

Tx: Weight loss for overweight or obese patients with lower extremity osteoarthritis coupled with both aerobic exercise as well as exercise to strengthen muscles proximate to the involved joint (ie, quadriceps muscle strengthening for knee osteoarthritis). More specifically, medial knee compartment osteoarthritis may benefit from heel inserts (5-10 degrees of lift), which help relieve the pressure on the medial compartment. Adaptive devices such as a cane in the hand contralateral to the painful joint may help by unloading forces on the knee or hip. Knee taping or bracing improves knee alignment, thus improving pain. Referral to physical or occupational therapy for active and passive range of motion exercise instruction or joint protection education may be helpful.

Rx: Acetaminophen is first-line pharmacologic therapy for osteoarthritis because it is safe, effective, and inexpensive. Patients with an inadequate response can be started on NSAIDs, preferably at the lowest effective dose to limit side effects (eg, gastrointestinal and renal toxicity, exacerbation of congestive heart failure and hypertension). Although cylcooxygenase-2-selective NSAIDs are somewhat less likely to cause gastrointestinal ulcers, they are not more effective than nonselective NSAIDs, are significantly more expensive, and are associated with an increased risk for adverse cardiovascular events.

Intra-articular glucocorticoids may be effective in providing pain relief and improving function. Successful injections provide pain relief for an average of 3 months.  Intra-articular injection may be particularly useful in patients who obtain no relief from acetaminophen and have contraindications to the use of nonsteroidal anti-inflammatory drugs (NSAIDs), such as chronic kidney disease, hypertension and a history of peptic ulcer disease.

Total joint arthroplasty should be considered for patients who do not adequately respond to nonsurgical methods. Replacement of the damaged joint restores normal biomechanics and often results in dramatic improvements in quality of life. 


Psoriatic arthritis

Hx: There are five patterns of joint involvement in psoriatic arthritis: involvement of the distal interphalangeal joints; asymmetric oligoarthritis; symmetric polyarthritis (similar to that of rheumatoid arthritis); arthritis mutilans (extensive osteolysis of the digits with striking deformity); and spondylitis (axial disease). Characteristic features of psoriatic arthritis include enthesitis (inflammation of sites where tendons or ligaments insert into bone), dactylitis (inflammation of an entire digit), and tenosynovitis (inflammation of the synovial sheath surrounding a tendon). 

Common involvement of DIP joints, with fusiform swelling of digits and skin and nail changes consistent with psoriasis.

Synovial and entheseal swelling; may involve the DIP joints; dactylitis (sausage digits) present.

Characterized by joint distribution and appearance similar to that of reactive arthritis. Predilection for distal interphalangeal joints, often with concomitant nail pitting and onycholysis.

CRX: Destructive arthritis with erosions and osteophytes; DIP involvement; “pencil-in-cup” deformity on hand radiograph; arthritis mutilans


Peripheral arthritis associated with IBD

Up to 20% of cases of IBD involve arthritis. The arthritis usually is nondestructive, involves the lower extremities, and reflects active bowel disease. May be indistinguishable from ankylosing spondylitis.


Reactive arthritis

Reactive arthritis occurs in both men and women, and enthesitis and oligoarthritis are common.

Hx: The classic triad of arthritis, urethritis, and conjunctivitis occurs in only about one third of patients. Manifests within 2 months of an episode of bacterial gastroenteritis or nongonococcal urethritis or cervicitis in a genetically predisposed patient.

Reactive arthritis was previously called Reiter syndrome, which referred to the coincidence of arthritis, conjunctivitis, and urethritis (or cervicitis). However, only about one third of patients have all three symptoms. Reactive arthritis usually affects the peripheral joints, often in the lower extremities, although inflammatory back pain also may be present.

Patients may also present with heel pain with enthesitis; keratoderma blennorrhagicum on the palms or soles; or circinate balanitis on the penis.

Differs from rheumatoid arthritis in that it is oligoarticular and asymmetric?

Presents as symmetric? inflammatory oligoarthritis, most often involving weight-bearing joints; may include tendon insertion inflammation (enthesitis).

Extra-articular manifestations include conjunctivitis, urethritis, stomatitis, and psoriaform skin changes (hyperkeratotic lesions on the palms and soles). Infection with Salmonella, Shigella, Yersinia, Campylobacter, or Chlamydia species within 3 wk prior to onset of initial attack.


Infectious arthritis

Usually monoarticular but may be oligoarticular; may be migratory; more often affects large joints. Patients present with hot, red, and swollen joints with limited range of motion. Joint fluid analysis is essential. Septic arthritis may develop in joints affected by rheumatoid arthritis.

Characterized by fever, arthritis, and exquisite joint tenderness. May occur as a complication of other arthritis syndromes. The source of infection (skin, lungs) often is evident. Usually occurs in previously abnormal joints.


Systemic lupus erythematosus (SLE)

Clinically indistinguishable from the arthritis of rheumatoid arthritis; however, the arthritis in systemic lupus erythematosus is non-nodular and nonerosive.

Acute arthritis, especially monoarthritis, in an immunosuppressed patient with systemic lupus erythematosus requires a diligent workup to rule out infectious arthritis. Search for opportunistic infections in addition to the common pathogens.



Viral arthritis

Arthritis and rash lasting days to weeks, often after a flu-like illness. 

Possible causes include Epstein-Barr virus, adenovirus, human parvovirus B19, rubella, HIV, HBV, and HBC.

Patients may have morning stiffness, with symmetric involvement of the hands and wrists; they also may be RF-positive (a pseudo–rheumatoid arthritis pattern). Most cases (except those caused by human parvovirus B19) resolve in 4-6 wk.


Trochanteric bursitis

Bursitis results when a bursa becomes inflamed (usually from trauma or an overuse syndrome) or infected

Hx: Pain and tenderness over the greater trochanter; pain may radiate down the lateral aspect of the thigh. Patients describe pain when lying on their side or swinging their leg into a car. 

Px: Hip range of motion is normal; although patients may indicate that they believe they are having pain in the joint, nonarticular pain is often worse with active range of motion and is localized away from the joint on palpation.


Pes Anserine bursitis

Most commonly a confounding cause of knee pain in patients with medial knee osteoarthritis, but also occurs in the setting of overuse (such as running).

Pain and tenderness over the anteromedial aspect of the proximal tibia below the joint line of the knee.

Pain is worse with climbing stairs and frequently worsens at night.

Px: Tenderness is elicited at the level of the tibial tuberosity (approximately 3.8 cm [1.5 in] below the level of the medial joint line).  Swelling may be present at the insertion of the medial hamstring muscles. 


Iliotibial band syndrome

Knife-like lateral knee pain that occurs with vigorous flexion-extension activities of the knee

Hx: Most commonly occurs in young athletes such as runners or cyclists.  Patients often describe pain that radiates down the outside of the leg. 

Px: Pain to palpation along the band down to the knee. Stretching of the iliotibial band by adducting the knee often reproduces the pain.

Tx: Treated conservatively with rest and stretching exercises. 


Patellofemoral pain syndrome

The most common cause of knee pain in patients younger than age 45 years.  The pain is peripatellar and exacerbated by overuse (such as running), descending stairs, or prolonged sitting.

Hx: Anterior knee pain that is made worse with prolonged sitting and with going up and down stairs. 

Px: The pain is reproduced by applying pressure to the patella with the knee in extension and moving the patella both medially and laterally (patellofemoral compression test).


Prepatellar bursitis

Hx: Pain in the anterior aspect of the knee.

Often caused by recurrent trauma, such as repeated kneeling (“housemaid's knee”) but can also be caused by infection or gout.

Px: swelling, tenderness to palpation (usually localized near the lower pole of the patella), and erythema, 


de Quervain tenosynovitis

Caused by inflammation of the abductor pollicis longus and extensor pollicis brevis tendons in the thumb. It is usually associated with repetitive use of the thumb but can also be associated with other conditions, including pregnancy, rheumatoid arthritis, and calcium apatite deposition disease. The typical presentation is of pain on the radial aspect of the wrist that occurs when the thumb is used to pinch or grasp. Examination findings include localized tenderness over the distal portion of the radial styloid process and pain with resisted thumb abduction and extension. 


Ganglion cysts

Swellings that overlie either joints or tendons most typically on the dorsal surface, develop as a result of chronic irritation of the wrist. If the cyst is not painful, no intervention is required.


Enteropathic Arthritis

Arthritic conditions associated with gastrointestinal disease.  

Up to 20% of patients with Crohn disease or ulcerative colitis develop inflammatory joint disease. Polyarthritis that resembles seronegative rheumatoid arthritis develops in 20% of these patients, whereas 10% to 15% of these patients develop spondylitis and sacroiliitis. The risk for inflammatory joint disease associated with Crohn disease or ulcerative colitis increases in patients with more advanced colonic conditions and additional concomitant extraintestinal manifestations, including abscesses, erythema nodosum, uveitis, and pyoderma gangrenosum. Peripheral arthritis associated with inflammatory bowel disease (IBD) is often classified as one of two types. In type I arthropathy, the peripheral arthritis tends to be acute, affects only a few joints, tends to occur early in the course of IBD, may worsen with flares of IBD, and is often self-limited. In type II arthropathy, more joints tend to be involved and symptoms may be migratory. Joint pain is usually not related to IBD activity, and symptoms may wax and wane over years. In patients with arthritis sensitive to flares of IBD, treating the underlying gastrointestinal disease is indicated. Additional treatment for sacroiliitis and peripheral joint disease is otherwise symptomatic.