Diseases That Mimic Rheumatoid Arthritis

A number of diseases mimic the symptoms of rheumatoid arthritis (RA), an autoimmune form of arthritis. These include bacterial joint infections, inflammatory diseases, other autoimmune diseases, and other forms of arthritis.

Ruling out conditions that mimic RA is central to the diagnosis of RA. To do so, your healthcare provider will not only order tests that point to RA as the cause but also order tests to exclude other diseases like Lyme disease, lupus, or fibromyalgia.

Even if you've been diagnosed with RA, your healthcare provider may want to investigate other possible causes if you are not responding to RA treatment or if there is a chance that another disease is co-occurring with RA (referred to as a comorbidity).

This article describes 14 conditions that mimic rheumatoid arthritis along with comorbid conditions that commonly occur alongside RA.

Osteoarthritis

Osteoarthritis (OA), is a degenerative joint disease that can be similar to RA. It is the most common form of the disease, often referred to as "wear-and-tear arthritis."

There are some key differences between OA and RA:

• OA does not cause systemic (whole-body) inflammation, while RA does.
• OA tends to start at an older age (55 and over) compared to RA (30 and over).
• OA affects different joints than RA (like those of the fingers).
• OA affects joints with no specific pattern, while RA affects joints symmetrically (on the same sides of the body at the same time).
• OA pain typically gets worse with activity, while RA pain generally improves.

Blood and imaging tests can help ensure an accurate diagnosis. These include:

• Rheumatoid factor (RF): A blood test that detects and measures a type of antibody associated with RA and other autoimmune diseases
• Anti-citrullinated peptide (anti-CCP) antibodies: A blood test that detects antibodies more specific to RA
• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP): Blood tests that detect generalized inflammation (which would be seen with RA but not OA)

RA and OA also have distinctly different patterns on X-ray which help determine which type of arthritis is involved.

Lupus and Scleroderma

Systemic lupus erythematosus (lupus) and scleroderma are two autoimmune diseases that can mimic rheumatoid arthritis. Autoimmune diseases are those in which the body's immune system attacks its own cells and tissues.

With lupus, the attack is systemic (affecting multiple organ systems are affected), while scleroderma primarily affects the skin and joints.

Lupus and scleroderma differ from RA in that the tendons and ligaments surrounding the joints are the primary targets of the assault. With RA, the inflammation occurs in the lubricating fluid within joint spaces (called synovial fluid), leading to the progressive destruction of joint cartilage.

Because RF and anti-CCP tests are also typically elevated with RA, lupus, and scleroderma, a third test, called the antinuclear antibodies (ANA) test, may help differentiate the diseases. With lupus and scleroderma, ANA results will almost invariably be high, while the results with RA can vary.

Other signs of lupus and scleroderma uncommon with RA include:

• Raynaud’s phenomenon: A symptom characterized by painfully cold fingers and toes
• Digestive symptoms: Including dysmotility (reduced movement of the gastrointestinal tract) and ascites (abdominal distention)
• Tightening and hardening of the skin: The defining symptom of scleroderma
  

Sjögren's Syndrome

Sjögren's syndrome (SjS) is another autoimmune disease that primarily affects moisture-producing glands called the salivary and lacrimal glands. SjS can also affect other organ systems as well, most notably the joints.

Joint pain is one of the more common symptoms of SjS. Multiple joints are typically affected, causing sudden and severe episodes of pain, swelling, and tenderness. As with RA, joints on both sides of the body are affected at the same time.

With SjS, the joints of the knees, wrists, and fingers are most commonly affected. With RA, the joints of the hands, wrists, and feet are mainly affected alongside with shoulders, elbows, knees, and ankles.

Sjögren’s syndrome can be hard to distinguish from RA because many of the standard tests will deliver the same or similar results. Moreover, many people with SJS also have RA, further complicating the diagnosis.

One test that can help differentiate the diseases is the anti-SSA/Ro test (also known as the Sjögren antibody test). While the test will show elevated anti-SSA antibodies in about 50% of people with SjS, they may be elevated with other autoimmune diseases, such as lupus and even RA.

The differentiation of SjS and RA requires an expert review of the various tests and symptoms. For example, SjS is characterized by sicca, a disruptive symptom that causes extreme and persistent dryness of the mouth and eyes. Sicca is not a feature of RA.

Psoriatic Arthritis

Psoriatic arthritis (PSA) is a type of arthritis linked to the autoimmune skin condition psoriasis. PSA can closely mimic RA, but can often be differentiated through blood tests.

Since high levels of RF and anti-CCP are typically present in RA, these results are considered seropositive.

PsA can have low levels of RF but no anti-CCP antibodies, making these indicators seronegative.

Both RA and PsA can start in the fingers and toes. However, PsA and other spondyloarthropathies are more likely to go on to affect the spine and the sacroiliac joints than RA.

Other key characteristics of PsA that help differentiate it from RA include:

• Asymmetrical joint involvement
• Absence of small-joint disease
• Inflammation where joints insert into bones (enthesitis)
• A sausage-like appearance of fingers or toes (dactylitis)
• Psoriatic rash, which may or may not be present

Viral Arthritis

Viral infections such as rubella, parvovirus B19, HIV, and hepatitis B and C can cause pain and swelling in multiple joints (polyarthritis) and present in a way that's clinically similar to rheumatoid arthritis.

Viral arthritis can often be distinguished from RA by a rash and a history of exposure to specific viruses. For example, recent travel to Italy, India, the Indian Ocean islands, or the Caribbean could lead to exposure to the mosquito-borne alphavirus chikungunya, which presents as joint pain, fever, and a rash.

Your healthcare provider can take blood work to rule out different viral and bacterial causes of joint pain. Treatment for viral arthritis is normally focused on pain management. And HIV-triggered arthritis can be relieved with combination antiretroviral therapy.

Most cases of viral arthritis resolve on their own after several weeks.

Lyme Disease

Lyme disease is a tick-borne illness caused by the bacteria Borrelia burgdorferi or Borrelia mayonii. It presents with joint pain and swelling but can be mistaken for RA. The first sign of Lyme disease is a bull's-eye rash (present in 70% of cases) that appears three to 30 days after a bite from an infected tick.

Left untreated, Lyme disease results in chronic arthritis with severe joint pain and swelling, particularly in the knees and other large joints.

Other signs of Lyme disease that aren't present in RA include:

• Severe headaches and neck stiffness
• Loss of muscle tone or drooping on one or both sides of the face
• Intermittent pain in tendons, muscles, joints, and bones
• Heart palpitations or an irregular heartbeat
• Dizziness or shortness of breath
• Shooting pains, numbness, or tingling in the hands or feet

Early treatment of Lyme disease with antibiotics typically results in complete recovery, though symptoms can linger for up to six months. A delay in antibiotic treatment can make the disease more difficult to treat and may result in chronic symptoms and pain, so it's important that any symptoms be investigated early.

Fibromyalgia

Fibromyalgia, a chronic pain condition, can be misdiagnosed as RA or another rheumatic condition. Both RA and fibromyalgia can involve symmetrical joint pain and stiffness, but with fibromyalgia, the pain occurs at rest and is not exacerbated by joint use.

Imaging studies are useful for distinguishing the conditions because synovitis (inflammation of joint lining) is present with RA and absent with fibromyalgia.

In addition, markers for inflammation and autoantibody testing (like RF and anti-CCP) are negative in fibromyalgia because symptoms aren't caused by an autoimmune response.

Fibromyalgia also differs from RA because it causes:

• Fatigue and tiredness
• Brain fog
• Anxiety and depression
• Headaches
• Irritable bowel syndrome
• Numbness or tingling in the hands and feet
• Jaw pain and temporomandibular joint disorders (TMJ)
• Sleep problems

Fibromyalgia can be difficult to diagnose. There are no specific tests to confirm a diagnosis and, much like with RA, it is important to rule out other possible conditions.

Gout

Crystal-deposition diseases like gout and pseudogout are often mistaken for RA. With these conditions, uric acid crystal deposits settle around affected joints, resulting in inflammation and tissue damage.

Gout tends to appear as painful, swollen joints associated with asymmetric inflammation in one or more fingers or toes. A gout attack commonly affects the large toe and lasts for three to 10 days.

Over time, gout attacks can become more frequent, last longer, and may not resolve. This can lead to chronic gouty arthropathy, which can cause erosions and joint destruction.

Calcium pyrophosphate deposition disease (CPPD) or pseudogout (false gout) is a type of arthritis that can present similarly to gout or RA but is distinguishable from acute gout attacks.

Tests your healthcare provider may perform to differentiate between gout, CPPD, and RA include blood tests for uric acid, imaging tests, and synovial fluid analysis.

Reactive Arthritis

A painful form of inflammatory arthritis, reactive arthritis is caused by a bacterial infection of the genitals or bowels. It commonly affects the heels, toes, fingers, low back, knees, or ankles.

Previously known as Reiter's syndrome, reactive arthritis is in the family of seronegative spondyloarthropathies. Symptoms generally appear within a month of a bout of diarrhea or a genital infection.

A blood test can identify bacterial infections, such as Chlamydia trachomatis, Campylobacter, Salmonella, Shigella, or Yersinia.

Bursitis

Bursitis is an inflammation of the small, fluid-filled sac (bursa) that acts as a cushion between a bone and other moving parts. Caused by overuse or injury, the condition causes joint pain and inflammation that can be mistaken for RA.

Bursitis typically affects only one joint at a time—commonly the knee, elbow, or shoulder—and does not have the systemic symptoms of RA.

Diagnosis is based on physical examination and imaging tests such as X-rays or MRIs. Your healthcare provider may sample fluid from the swollen area to rule out an infection as well.

Sarcoidosis

Sarcoidosis, an inflammatory disease that typically affects the lungs, skin, or lymph nodes, can mimic RA. Characterized by tiny, grain-like lumps (granulomas), sarcoidosis can manifest with synovitis in several joints. RF can be positive with this condition.

Like RA, sarcoidosis onset typically occurs between ages 30 and 50.

Other characteristics of sarcoidosis that help to distinguish it from RA include:

• Cough
• Shortness of breath
• Weight loss
• Night sweats
• Fatigue

Sarcoidosis is formally diagnosed through biopsy.

Polymyalgia Rheumatica and Giant Cell Arteritis

Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are closely linked inflammatory conditions that almost always occur in people over 50 years old. These conditions affect joints and might mimic RA.

PMR causes muscle pain and stiffness in the shoulders, upper arms, hip area, and sometimes the neck. GCA is a type of vasculitis that can cause symmetrical pain and tenderness in multiple joints. In addition, people with vasculitis often test positive for rheumatoid factor.

A key difference is that GCA commonly presents with headaches. A detailed medical history can help distinguish PMR or GCA from RA.

In some cases, a diagnosis of vasculitis may depend on observation of the disease over time, particularly if complications develop.

Hemochromatosis

Hemochromatosis is a condition in which too much iron builds up in the body, especially in the skin, liver, heart, pancreas, and joints. It's most often caused by a mutation in the HFE gene. About 1 in 225 people of Northern European ancestry have two copies of this gene and are at risk of developing hemochromatosis. The condition is uncommon in people of Asian or African ancestry.

Other causes include severe liver disease and receiving multiple blood transfusions.

Hemochromatosis can cause arthritis, among other problems. The joint pain notably affects the knuckles of the index and middle fingers. The joints may be swollen and have reduced range of motion, but are not inflamed.

Large joints such as the knees, hips, ankles, elbows, and shoulders may also be painful. The presence of pain in the ankles and wrists can help healthcare providers distinguish hemochromatosis from other causes of arthritis.

People with hemochromatosis also have other symptoms, including:

• Fatigue and weakness
• Weight loss
• Bronze, gray, or darkened skin color
• Abdominal pain
• Loss of sex drive or erectile dysfunction

The condition can lead to a range of complications due to the organ damage the iron causes, such as liver disease or cancer, heart failure, diabetes, and hypothyroidism.

Dual Diagnosis

You may be so used to living with RA that you chalk up any change in your symptoms to the disease, rather than another possible cause.

If you are experiencing an unusual persistence of or increase in your RA symptoms, or if new ones appear, check in with your healthcare provider. Additional diagnoses can be considered and, at the very least, you can be evaluated to see if your RA treatment plan needs to be modified.

While it's possible that you could also have any of the common RA mimics, the most common RA comorbidities—which may or may not have similar symptoms—include:

• Cardiovascular disorders
• Gastrointestinal disease
• Renal diseases
• Pulmonary diseases
• Infections
• Osteoporosis
• Tumors
• Depression

Summary

Joint pain, a common symptom of many conditions that can mimic rheumatoid arthritis, may complicate the diagnosis. If you aren't improving with treatment, talk to your healthcare provider. You might need additional testing or a referral to a rheumatologist or other specialist. Ensuring an accurate diagnosis is essential for finding a treatment that works for you.