Rheumatoid Arthritis Differential Diagnosis

Part of diagnosing rheumatoid arthritis (RA) involves ruling out other conditions that mimic RA, such as fibromyalgia, Lyme disease, and osteoarthritis. Diagnosis involves a physical examination, a review of medical history, blood work, and imaging studies.  

Rheumatoid arthritis (RA) is a type of inflammatory arthritis. RA causes chronic inflammation that attacks the lining of the joints (the synovium). As a result, the joints may get red, warm, swollen, and painful.

If left untreated or if your condition is unresponsive to therapy, you can lose joint function and the ability to carry out daily tasks. Uncontrolled inflammation may lead to other health risks, including cardiovascular disease. Early recognition and treatment are vital to controlling the disease and preventing joint damage and disability.  

RA is an autoimmune disease in which the immune system malfunctions and starts to attack healthy tissues, mainly the synovium. It isn't known what causes the immune system to respond in this way, but certain factors increase your risk for RA. Risk factors include genetics and family history, being female, being overweight, and smoking.

This article will discuss differential diagnoss for RA, differentiating factors, RA symptoms, and more.  

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Differential Diagnosis for Rheumatoid Arthritis 

A differential diagnosis is a method of analyzing a patient's medical history, physical examination, lab work, imaging, and additional testing to arrive at a correct diagnosis. It also involves distinguishing a specific condition from others with similar symptoms.  

Fibromyalgia  

Fibromyalgia is a disorder that causes widespread musculoskeletal pain. RA and fibromyalgia share some similar symptoms, including pain, sleep troubles, fatigue, anxiety, and depression.

Their causes, however, are very different. RA Is an autoimmune disease that causes the immune system to attack the joints. Researchers believe fibromyalgia causes abnormal pain perception processing, meaning the pain becomes amplified because of how the brain and spinal cord process it.  

These two conditions progress differently. RA can flare up at times and worsen without appropriate treatment. Like RA, fibromyalgia is a lifelong condition, but it is not progressive. It does not worsen over time or cause damage to the joints, muscles, or organs.  

Fibromyalgia and RA Together

Researchers estimate that 18%–24% of people living with rheumatoid arthritis also have fibromyalgia. This can affect how their healthcare provider assesses their RA disease activity and may result in overtreatment.

Lyme Disease  

Lyme disease is a bacterial infection from the bite of an infected tick. Early symptoms of Lyme disease are a rash, fatigue, fever, and headache.

Lyme disease is sometimes confused with RA, and both of these conditions can become severely worse if not properly treated. Joint symptoms of Lyme disease resolve with treatment. With RA, joint symptoms can improve with treatment, but they also can return. Also, RA has no cure.

Additional ways to tell these conditions apart are:  

  • Lyme disease causes arthritis symptoms in one or two joints on either side of the body, which come and go.
  • RA is symmetrical, meaning it causes symptoms in the same joints on both sides of the body. It also causes morning pain and stiffness.
  • RA affects people with specific risk factors, whereas anyone can develop Lyme disease if they are bitten by a tick.

Osteoarthritis

Osteoarthritis (OA) is the most common type of arthritis. A primary difference between OA and RA is the cause of joint symptoms. OA results from wear and tear of the joints, and RA occurs when the immune system malfunctions and attacks the joints.

OA and RA share some similar symptoms. However, RA affects multiple joints on both sides of the body. OA will only affect a few joints on one side of the body.

RA also causes systemic (body-wide) inflammation, which leads to symptoms like fatigue, fever, and malaise (a general unwell feeling). OA can sometimes cause inflammation, but it tends to be limited to affected joints.

Polymyalgia Rheumatica

Polymyalgia rheumatica (PMR) is an inflammatory disorder that causes muscle pain and stiffness. It mainly affects the shoulders and hips and is common in people over age 65.

PMR can sometimes be mistaken for RA, especially when RA is limited and affects someone over age 50. Joint symptoms in PMR tend to be milder and asymmetric (affecting one side of the body). 

Psoriatic Arthritis

Psoriatic arthritis (PsA) is a type of inflammatory arthritis affecting some people with psoriasis, an autoimmune skin condition. PsA causes inflammation of the joints and the entheses—the areas where tendons and ligaments meet bone. It also causes a skin rash that appears as raised red patches of skin covered in a white buildup of dead skin cells.  

PsA and RA share similar symptoms, mainly systemic ones, like fatigue and malaise. PsA is typically asymmetrical, while RA is symmetrical.

Other differences include:

  • Low-back pain: PsA causes spine inflammation, while RA rarely affects the spine.
  • Inflammation of the distal joints: PsA frequently affects the distal joints close to the fingernails and toenails. On the other hand, RA involves the metacarpophalangeal joints (the joints that connect the fingers to the hands).
  • Enthesitis: PsA causes inflammation of the entheses, most commonly in the heels, the bottom of the feet, and elbows.

Sarcoidosis  

Sarcoidosis causes inflammation of the lungs, skin, and lymph nodes. It leads to granulomas, tiny, grain-like lumps. People with sarcoidosis might experience chronic arthritis similar to what is seen in RA. Sarcoidosis's joint symptoms can affect the knees, ankles, wrists, hands, and fingers.  

Specific blood work markers and a chest X-ray can help a healthcare provider distinguish it from RA. Abnormalities can be seen on chest imaging in more than 90% of people with thoracic involvement of sarcoidosis.

Sjögren's Syndrome

Sjögren's syndrome is an autoimmune disease that affects the mucous membranes and the moisture-producing glands of the eyes and mouth, leading to decreased tears and saliva. About half of the people with Sjögren's also have another autoimmune disease like RA.

Symptoms of RA and Sjögren's syndrome can overlap. Overlapping symptoms include:  

  • Swollen joints and muscles
  • Dry skin and rashes
  • Brain fog
  • Numbness and tingling of the arms and legs

Systemic Lupus Erythematosus  

Like RA, systemic lupus erythematosus (SLE) is an autoimmune disease that shares some symptoms with RA. Shared symptoms include joint pain and inflammation, and fatigue.

In addition, both conditions affect the same joints, including the smaller joints of the fingers, hands, wrists, and feet. Symmetrical symptoms are also common in both diseases. However, joint damage is rare in people who have lupus.

SLE is different from RA because SLE affects the skin, while RA usually does not. An SLE typically presents with a butterfly-shaped rash on the nose and cheeks. People with SLE are also more likely to experience inflammation of their heart and lungs than people with RA. SLE can also cause damage to the kidneys.

In a person who has lupus and symptoms of arthritis, antinuclear antibody levels are elevated while markers for RA are negative. This can help point towards a diagnosis of lupus.

Differentiating Factors  

RA has some features that help distinguish it from osteoarthritis and other types of inflammatory arthritis.  

Symptoms of RA affect four or more of the small joints. In RA, joint pain starts in the fingers. Symptoms of RA are often symmetrical, involving the same joints on both sides of the body. Morning stiffness lasting 30 minutes or longer is common in RA. Some people with RA also experience rheumatoid nodules—nonpainful bumps under the skin.

RA inflammation can cause additional problems beyond the joints, such as with the eyes, skin, lungs, or heart. RA also increases the risk for infections, including pneumonia, sinus infections, and urinary tract infections.

People with RA have an increased risk for additional autoimmune conditions, including Sjögren's disease and SLE, and complications like depression and carpal tunnel syndrome.

There is no single lab test to diagnose RA, so healthcare providers will utilize guidelines and a point system to get an accurate diagnosis. The American College of Rheumatology and the European League Against Rheumatism have established classification criteria for diagnosing RA.

These guidelines are a minimum standard for signs and symptoms of RA that must be present for a diagnosis of RA to be made. The scoring system includes affected joints, non-joint symptoms of RA, and blood work. 

Different blood tests can help diagnose or rule out RA, including:  

Your healthcare provider may also order X-rays, ultrasound (imaging using sound waves), magnetic resonance imaging (MRI), or other imaging tests to check for signs of RA or when testing does not offer enough information to diagnose or rule out RA.

Rheumatoid Arthritis Symptoms  

RA always affects the joints. Inflammation often leads to pain, swelling, and tenderness of the joints. Additional symptoms of RA include: 

  • Joint stiffness
  • Redness and warmth of the joints
  • Fatigue
  • Muscle aches
  • Decreased appetite
  • Malaise
  • Depression

RA usually starts in the hands, especially in the finger joints. Other commonly affected joints are the elbows, wrists, ankles, feet, toes, hips, knees, shoulders, and jaw.  

While rare, RA can affect the voice box, called the cricoarytenoid joints. Inflammation of the voice box can make the voice hoarse or cause you to lose your voice.  

Additional symptoms of RA might include:  

  • Redness and dryness of the eyes
  • Blood vessel inflammation called rheumatoid vasculitis
  • Rheumatoid nodules
  • Inflammation of the lungs, a condition called pleurisy
  • Inflammation of the lining around your heart (called pericarditis) or heart muscle (called myocarditis) 

When to Call a Healthcare Provider

Muscle and joint pain are common in inflammatory arthritis conditions like RA. You should see your primary healthcare provider if you have pain that lasts for more than a few days. A provider can evaluate whether you are experiencing temporary pain from an injury or an inflammatory cause.

Your provider can also refer you to a rheumatologist (a specialist in treating conditions of the muscles, bones, and joints) if necessary.

Additional symptoms that warrant a visit to a rheumatologist include:

  • New pain in multiple joints
  • Muscle or joint pain accompanied by fever, fatigue, or rash
  • Joint pain or stiffness first thing in the morning that lasts more than a half-hour

Don't delay treatment for ongoing or worsening joint, bone, or muscle pain. RA and other inflammatory arthritis types can lead to permanent damage if not managed promptly and appropriately.

How to Ensure an Accurate Diagnosis  

The sooner RA is diagnosed, the sooner you can start treating the condition. But diagnosing RA can be a challenge, and you may have to see multiple healthcare providers before a correct diagnosis is made.  

RA signs and symptoms can vary, so the disease is sometimes hard to recognize, especially early on. For example, one person might experience swelling of the finger joints in both hands while another person might experience fatigue, fever, and inflamed knees that start suddenly and quickly worsen.

Keeping a record of all possible symptoms, even if they seem unrelated, can help you point your healthcare provider towards the correct diagnosis. Ensure your medical record is complete with all past and current health issues and family history.

During your medical appointment, your healthcare provider will want to know what symptoms you are experiencing, their severity, when they began, how often you experience them, and how they have changed over time. They will also ask about other medical problems, current medications, and family history of RA and other autoimmune diseases.

During the physical exam, your healthcare provider will examine your joints to look for signs of inflammation. They will also measure the range of motion of affected joints, joint strength, and tenderness by pressing over an affected joint to see if it causes pain.

Your healthcare provider will also order blood tests to look for markers of RA, as well as imaging tests. These will all factor into the diagnosis, which should be based on established criteria. It is always appropriate to ask for a second opinion from another healthcare provider.

Summary  

Rheumatoid arthritis (RA) is a type of inflammatory arthritis that causes inflammation of the lining of the joints. It causes redness, warmth, swelling, and pain in the joints.

Diagnosing RA involves ruling out other conditions that cause similar symptoms of RA, including fibromyalgia, SLE, Lyme disease, and osteoarthritis. Diagnosis of RA includes a physical exam, medical history review, blood work, and imaging studies.

A Word From Verywell 

While it is difficult to predict the course of rheumatoid arthritis, advances in medicines and other treatments for RA have improved disease prognosis. This is especially true when a person gets an early diagnosis and receives early and aggressive treatment.

The outlook for people with RA is better than it has ever been, and many people can experience disease remission and live a long life with the condition.

Frequently Asked Questions

  • What can be mistaken for rheumatoid arthritis?

    Many different conditions can cause similar symptoms to rheumatoid arthritis, including fibromyalgia, SLE, psoriatic arthritis. There is also an overlap of symptoms between RA and these conditions, including joint pain, stiffness, and fatigue.

  • What is the difference between polymyalgia rheumatica and rheumatoid arthritis?

    Polymyalgia rheumatica and rheumatoid arthritis sometimes present with similar symptoms. However, polymyalgia rheumatica mainly affects people over age 65 and commonly affects the shoulders and hips. Joint symptoms of polymyalgia rheumatica are milder than RA and generally affect only one side of the body.


  • What are some of the early symptoms of rheumatoid arthritis?

    Rheumatoid arthritis will start gradually and worsen over time. Early signs might include fatigue, malaise, reduced joint range of motion, and joint problems, including pain, tenderness, swelling, warmth, redness, and stiffness, in the smaller joints of the hands and feet.

  • How is rheumatoid arthritis diagnosed?

    An accurate diagnosis of rheumatoid can be made by reviewing symptom history, medical and family history, a physical examination of joints, blood work, and imaging.

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10 Sources
Verywell Health uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. Centers for Disease Control and Prevention. Rheumatoid arthritis (RA).

  2. MedlinePlus. Differential diagnosis.

  3. Sluka KA, Clauw DJ. Neurobiology of fibromyalgia and chronic widespread painNeuroscience. 2016;338:114-129. doi:10.1016/j.neuroscience.2016.06.006

  4. Zhao SS, Duffield SJ, Goodson NJ. The prevalence and impact of comorbid fibromyalgia in inflammatory arthritis. Best Pract Res Clin Rheumatol. 2019;33(3):101423. doi:10.1016/j.berh.2019.06.005

  5. Arvikar SL, Crowley JT, Sulka KB, Steere AC. Autoimmune arthritides, rheumatoid arthritis, psoriatic arthritis, or peripheralspondyloarthritis following Lyme disease. Arthritis Rheumatol. 2017;69(1):194-202. doi:10.1002/art.39866

  6. Baker JF. Diagnosis and differential diagnosis of rheumatoid arthritis. UpToDate.

  7. Ganeshan D, Menias CO, Lubner MG, Pickhardt PJ, Sandrasegaran K, Bhalla S. Sarcoidosis from head to toe: What the radiologist needs to know. Radiographics. 2018;38(4):1180-1200. doi:10.1148/rg.2018170157

  8. American College of Rheumatology. Sjogren's syndrome.

  9. Johns Hopkins Arthritis Center. How is lupus diagnosed?

  10. England BR, Tiong BK, Bergman MJ, Curtis JR, Kazi S, Mikuls TR, O'Dell JR, Ranganath VK, Limanni A, Suter LG, Michaud K. 2019 Update of the American College of Rheumatology recommended rheumatoid arthritis disease activity measures. Arthritis Care Res (Hoboken). 2019 Dec;71(12):1540-1555. doi:10.1002/acr.24042