RA is a chronic, autoimmune inflammatory disease that primarily attacks the lining of the joints (synovium). This leads to persistent pain, stiffness, and swelling, typically affecting the small joints of the hands and feet in a symmetrical pattern. Because joint pain is common, the initial presentation of RA can be difficult to distinguish from numerous other diseases. Many conditions mimic RA by causing similar symptoms of joint inflammation or stiffness, but they arise from different underlying causes, such as distinct autoimmune processes, infections, or mechanical wear. Distinguishing between these conditions is critical because the treatment strategies for each are highly specific.
Inflammatory Conditions Lacking RA-Specific Antibodies
A major group of conditions mimicking RA are the seronegative spondyloarthropathies, which cause joint inflammation but typically test negative for Rheumatoid Factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies.
Psoriatic Arthritis (PsA) is a prominent example, often presenting with asymmetrical joint pain. PsA is distinguished by involvement of the distal interphalangeal (DIP) joints, which are typically spared in classic RA. It also features dactylitis, a painful, diffuse swelling of an entire finger or toe, often called a “sausage digit.” A history of psoriasis or nail changes like pitting provides strong clues toward PsA.
Ankylosing Spondylitis (AS) is another seronegative condition targeting the axial skeleton, specifically the sacroiliac joints and the spine. AS causes characteristic inflammatory back pain that is worse in the morning and improves with exercise, distinct from RA’s peripheral joint focus. Reactive Arthritis develops following an infection, often in the gastrointestinal or genitourinary tract. It typically affects a few large joints in an asymmetric pattern, often in the lower limbs, and is usually a transient condition that resolves after the infection clears.
Systemic Diseases with Joint Involvement
Several systemic connective tissue diseases present with joint pain, but their pathology involves multiple organ systems beyond the joints. Systemic Lupus Erythematosus (SLE), or lupus, is a prime example where joint pain and inflammation are common. Unlike RA, the arthritis in lupus is typically non-erosive, meaning it does not cause the permanent bone and cartilage destruction seen in untreated RA. Distinguishing features are systemic manifestations, such as a characteristic malar or “butterfly” rash, kidney inflammation (lupus nephritis), or sensitivity to sunlight.
Scleroderma, or Systemic Sclerosis, also causes joint pain and stiffness. Its hallmark feature is the progressive hardening and thickening of the skin, often accompanied by Raynaud’s phenomenon (fingers turning white or blue in response to cold). The joint issues in scleroderma are often due to the tightening of the skin and tendons around the joint, rather than primary synovial inflammation.
Polymyositis and Dermatomyositis are inflammatory muscle diseases where muscle weakness is the main symptom, especially affecting the proximal muscles of the shoulders and hips. These conditions can cause a mild, non-erosive arthritis that may be symmetric like RA. However, the defining features are the significant muscle weakness and, for dermatomyositis, specific skin rashes, which differentiate them from RA.
Acute Infections and Crystal-Related Arthritis
Some conditions cause acute, severe arthritis that mimics the sudden onset of an RA flare but are driven by infection or metabolic imbalances. Viral arthritis, caused by viruses such as Parvovirus B19 or Hepatitis B and C, can produce a polyarthritis similar to early RA. This type of arthritis is usually self-limiting and transient, resolving once the viral infection is cleared, unlike chronic RA. Lyme disease, a bacterial infection transmitted by ticks, causes inflammatory arthritis typically affecting only one large joint, most commonly the knee, a pattern distinct from RA’s symmetrical involvement.
Crystal-related arthritides, such as Gout and Pseudogout, are characterized by the rapid onset of extreme joint pain, redness, and swelling. Gout is caused by the deposition of monosodium urate crystals, often starting in the big toe, and is diagnosed by finding needle-shaped crystals in the joint fluid. Pseudogout (Calcium Pyrophosphate Deposition or CPPD disease) involves the deposition of calcium pyrophosphate crystals, typically affecting larger joints like the knee or wrist. Both are differentiated from RA by their rapid onset, the intensity of the pain, and the microscopic identification of the specific crystals in the joint fluid.
Non-Inflammatory Pain and Degenerative Conditions
Conditions causing joint discomfort without the underlying autoimmune inflammation of RA can lead to misdiagnosis. Osteoarthritis (OA) is the most common form of arthritis and is fundamentally a mechanical “wear-and-tear” disease, not an autoimmune one. OA pain typically worsens with activity and improves with rest, the opposite of inflammatory RA pain, which is worse after periods of rest, such as in the morning. OA commonly affects the hips, knees, and the DIP joints of the fingers. Any swelling is firm and bony, reflecting cartilage loss, rather than the soft, fluid-filled swelling of RA.
Fibromyalgia is a chronic pain disorder characterized by widespread musculoskeletal pain, fatigue, and tenderness in soft tissues. It can be confused with the generalized discomfort of RA, but it does not cause inflammation, joint swelling, or joint damage. Fibromyalgia is considered a pain amplification disorder of the central nervous system. A physical examination reveals specific tender points, but no objective signs of synovitis, the defining feature of RA. The lack of true joint inflammation and normal joint appearance on imaging rule out RA.