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What Other Diseases "Masquerade" as Rheumatoid Arthritis? Part 1 – The Non-Infectious Group
Rheumatoid arthritis (RA) is the most common form of inflammatory arthritis and affects more than 2 million Americans. In many cases, it is not easy to make a diagnosis. There are more than 100 different types of arthritis. Most of them involve inflammation. When a patient goes to a rheumatologist for a diagnosis, a process of elimination takes place to arrive at the correct diagnosis. This process of elimination is called “differential diagnosis.”
Differential diagnosis can be a difficult endeavor because so many forms of arthritis, especially inflammatory forms of arthritis, look alike. In general, it is useful to divide the differential diagnosis of rheumatoid arthritis into two groups. The first group are non-communicable diseases to be considered, and the second group are conditions associated with infections.
Since the discussion is quite long, I decided to divide the article into two parts.
The following is a partial list of forms of inflammatory arthritis that may be seen and must be considered when evaluating a patient with inflammatory symptoms of arthritis that are not related to infection.
RA is an autoimmune chronic inflammatory disease that primarily affects peripheral joints (hands, wrists, elbows, shoulders, hips, knees, ankles and feet). It can also affect non-articular structures such as the lungs, eyes, skin and cardiovascular system.
RA can start slowly with nonspecific symptoms, including fatigue, malaise (feeling “blah”), loss of appetite, low-grade fever, weight loss, and vague joint pain, or it can have an explosive onset with inflammation involving multiple joints. Joint symptoms usually occur bilaterally – both sides of the body are equally affected – and symmetrically. Erosions – damage to the joint – can be seen on x-rays. In about 80% of cases, elevated levels of rheumatoid factor (RF) or anti-cyclic citrullinated antibodies (anti-CCP) are present in the blood. There appears to be a correlation between the presence of anti-CCP antibodies and erosions.
Juvenile rheumatoid arthritis (JRA) occurs in children under the age of 16. There are three forms of JRA, including oligoarticular (1-4 joints), polyarticular (more than 4 joints), and systemic disease or Still’s disease. The latter condition is associated with systemic symptoms — including fever and rash along with joint disease.
Polyarticular JRA has similar characteristics to adult RA. It causes about 30% of JRA cases. Most children with polyarticular JRA are RF negative and their prognosis is usually good.
Approximately 20% of patients with polyarticular JRA have elevated RF, and these patients are at risk for chronic, progressive joint damage.
Eye involvement in the form of inflammation – called uveitis – is a common finding in oligoarticular JRA, especially in patients who test positive for anti-nuclear antibodies (ANA), a blood test often used to screen for autoimmune disease. Uveitis may not cause symptoms, so careful screening should be performed in these patients.
SLE is an inflammatory, chronic, autoimmune disorder that can affect the skin, joints, kidneys, central nervous system, and blood vessel walls. Patients may have 1 or more of the following: a butterfly-shaped rash on the face, affecting the cheeks; rashes on other parts of the body; sensitivity to sunlight; mouth sores; joint inflammation; fluid around the lungs, heart, or other organs; kidney abnormalities; low white blood cell count, low red blood cell count, or low platelet count; inflammation of the nerves or brain; positive blood test results for ANA; positive blood test results for antibodies to double-stranded DNA or other antibodies.
Lupus patients may have significant inflammatory arthritis. As a result, lupus can be difficult to distinguish from RA, especially if other features of lupus are not present. Clues favoring the diagnosis of RA over lupus in a patient with multijoint arthritis include lack of features of lupus, radiographic erosions (joint damage), and elevation of RF and anti-CCP antibodies.
Polymyositis (PM) and dermatomyositis (DM) are types of inflammatory muscle disease. These conditions usually occur bilaterally (both sides are affected) with severe muscle weakness. In the case of DM, a rash is present. The diagnosis consists of the finding of the following: elevated levels of muscle enzymes in the blood [the two enzymes that are measured are creatine kinase (CPK) and aldolase]signs and symptoms, electromyography (EMG) – electrical test – change and positive muscle biopsy.
In addition, in many cases abnormal antibodies specific for inflammatory muscle disease may be elevated.
In both PM and DM, inflammatory arthritis may be present and may look like RA. Both inflammatory muscle disease and RA can affect the lungs. In RA, muscle function will usually be normal. Also, in PM and DM, erosive joint disease is unlikely. RF and anti-CCP antibodies are typically elevated in RA, but not in PM or DM.
SA – psoriatic arthritis, reactive arthritis, ankylosing spondylitis and enteropathic arthritis – are a category of diseases that cause systemic inflammation and primarily attack parts of the spine and other joints where tendons attach to bones. They can also cause pain and stiffness in the neck, upper and lower back, tendonitis, bursitis, heel pain and fatigue. They are called “seronegative” types of arthritis. The term ‘seronegative’ means that the rheumatoid factor test is negative. Symptoms of SA in adults include:
o pain in the back and/or joints;
o Morning stiffness;
o Sensitivity near the bones;
o Sores on the skin;
o joint inflammation on both sides of the body;
o Ulcers on the skin or in the mouth;
o Rash on the bottom of the foot; and
o eye inflammation.
Arthritis similar to that seen in RA may occasionally be present. A careful history and physical examination can often differentiate between these conditions, especially if an overt inflammatory disease is present (psoriasis, inflammatory bowel disease, etc.). In addition, RA rarely affects the DIP joints – the back row of the finger joints. If these joints are affected by inflammatory arthritis, a diagnosis of SA is possible. (Note of caution: a condition known as inflammatory erosive nodal osteoarthritis can also affect DIP joints). RF and anti-CCP antibodies are negative in SA, although, rarely, RF and anti-CCP antibodies may be elevated in cases of psoriatic arthritis.
Gout is caused by the deposition of monosodium urate (uric acid) crystals in the joint. Gouty arthritis has an acute onset, very painful, with signs of significant inflammation on examination (red, warm, swollen joints). Gout can affect almost any joint in the body, but it usually affects cooler areas including the toes, feet, ankles, knees and hands. The diagnosis is made by removing fluid from the inflamed joint and analyzing the fluid. Demonstration of monosodium urate crystals in the joint fluid is diagnostic, although the finding of elevated serum uric acid levels may also be helpful.
In most cases, gout is an acute disease of a single joint that is easy to distinguish from RA. However, in some cases, chronic erosive joint inflammation may develop where multiple joints are affected. And in cases where tophi (uric acid deposits) are present, it can be difficult to distinguish from erosive RA. However, analysis of joint crystals or tophi and blood tests should help distinguish gout from RA.
Calcium pyrophosphate deposition disease (CPPD), also known as pseudogout, is a disease caused by calcium pyrophosphate dihydrate crystal deposits in the joint. The presence of these crystals in the joints leads to significant inflammation. Making a diagnosis involves using:
o Detailed medical history;
o Withdrawing fluid from the joint to check for crystals;
o X-rays of the joints showing deposition of crystals in the cartilage (chondrocalcinosis); and
o Blood tests to rule out other diseases (eg RA or osteoarthritis).
In most cases, CPPD arthritis represents inflammation of one joint. In some cases, CPPD disease can manifest as chronic symmetric multi-joint erosive arthritis similar to RA. RA and CPPD disease can usually be distinguished by joint aspiration showing calcium pyrophosphate crystals and blood tests, including RF and anti-CCP antibodies, which are usually negative in CCPD arthritis. The complicating feature is that RA and CPPD can coexist!
Sarcoidosis is an inflammatory disorder of the joints. Most patients with this disease have lung diseases, and the next most common signs of the disease are eye and skin diseases. Although the diagnosis of sarcoidosis can be made only on clinical and X-ray examination, sometimes a tissue biopsy with evidence of “non-caseous granulomas” is necessary for the diagnosis.
Arthritis is present in 15% of patients with sarcoidosis, and in rare cases it can be the only sign of the disease. In acute sarcoid arthritis, joint disease usually begins quickly. It is symmetrical and involves the ankles, although the knees, wrists and hands can be affected. In most cases of acute diseases, lung and skin diseases are also present. Chronic sarcoid arthritis can be difficult to distinguish from RA. Although blood tests specific for RA, such as RF and anti-CCP antibodies, can help distinguish RA from sarcoidosis, in some cases a biopsy of joint tissue may be required for diagnosis.
Polymyalgia rheumatica (PMR) is a disease that leads to inflammation of the tendons, muscles, ligaments and tissues around the joints. It is manifested by severe muscle aches, pains, morning stiffness, fatigue and in some cases fever. It can be associated with temporal arteritis (TA), also known as giant cell arteritis, a related but more serious condition in which inflammation of the large blood vessels can lead to blindness and aneurysms. Also, an unusual syndrome can occur where using the arms and legs leads to spasms due to insufficient blood flow (limb claudication). PMR is diagnosed when there is a clinical picture with elevated inflammatory markers (ESR and/or CRP). If temporal arteritis is suspected (headache, changes in vision, claudication of limbs), a biopsy of the temporal artery may be necessary to prove inflammation of the blood vessels.
PMR and TA can present with symmetrical RA-like inflammatory arthritis. These diseases can usually be distinguished by a blood test. In addition, headaches, visual changes, and large muscle pain are not common in RA, and if present, PMR and/or TA should be considered.
In the second part of this article, I will discuss the infectious diseases that should be considered in the differential diagnosis of rheumatoid arthritis. When RA is suspected, it is crucial to consult a specialist rheumatologist.
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