There are more than 100 different kinds of arthritis. Most of them involve inflammation. When a patient goes to a rheumatologist to get a diagnosis, there is a process of elimination in order to arrive at the proper diagnosis. This process of elimination is called “differential diagnosis.”
Differential diagnosis can be a difficult undertaking because so many forms of arthritis, particularly inflammatory forms of arthritis look alike. The following is a list of types of inflammatory arthritis that can be seen and must be considered when evaluating a patient with inflammatory symptoms of arthritis.
Rheumatoid Arthritis (RA)
RA is an chronic, autoimmune, inflammatory disease, that may affect any joint in the body but preferentially attacks the peripheral joints (fingers, wrists, elbows, shoulders, hips, knees, ankles, and feet. It can also affect non-joint organ systems such as the lung, eye, skin, and cardiovascular system. The onset of RA may be insidious-slow- with nonspecific symptoms, including fatigue, malaise, loss of appetite, low-grade fever, weight loss, and vague aches and pains, or it may have an abrupt onset with inflammation involving multiple joints. The joint symptoms usually occur bilaterally and are symmetric. Damage to joints- called “erosions” can be seen with magnetic resonance imaging early on or by x-ray later in the course of disease. Approximately 80% of patients with RA will have elevated levels of rheumatoid factor (RF) or anti-CCP antibodies.
Juvenile Rheumatoid Arthritis (JRA)
JRA describes a group of arthritic conditions that occur in children under the age of 16. Three forms of JRA exist, including oligoarticular (1-4 joints), polyarticular (> 4 joints), and systemic-onset or Still’s disease. The latter is associated with significant internal organ involvement and may also present with fever and rash in addition to joint disease. Polyarticular JRA is considered to be the type that is most similar to adult RA, and is responsible for approximately 30% of cases of JRA. Most children with polyarticular JRA are negative for RF and their prognosis is usually good. Roughly, 20% of polyarticular JRA patients will have elevated RF, and these patients appear to be at more risk for chronic, progressive joint destruction and damage. Uveitis- an inflammatory condition of the eye- is a common finding in oligoarticular JRA, especially in patients who are antinuclear antibody (ANA) positive. The dangerous feature of uveitis is that it can cause relatively few symptoms so careful screening is recommended in order to avoid blindness.
Systemic Lupus Erythematosus (SLE)
SLE is a chronic inflammatory autoimmune disorder that can involve the skin, joints, kidneys, brain, and blood vessel walls. At least 4 of the following symptoms which have been formulated by the American College of Rheumatology are generally present for a diagnosis to be made:
Red, butterfly-shaped rash on the face, affecting the cheeks;
Typical skin rash on other parts of the body;
Sensitivity to sunlight;
Mouth sores;
Joint inflammation (arthritis);
Fluid around the lungs, heart, or other organs;
Kidney dysfunction;
Low white blood cell count, low red blood cell count due to hemolytic anemia, or low platelet count;
Nerve or brain dysfunction;
Positive results of a blood test for ANA; and
Positive results of a blood test for antibodies to double-stranded DNA or other antibodies including anti-Smith antibodies or antiphospholipid antibodies.
Patients with lupus can have significant inflammatory arthritis. That is why lupus can be difficult to distinguish from RA, especially if other signs and symptoms of lupus are minimal.
Inflammatory Muscle Disease
Polymyositis (PM) and dermatomyositis (DM) are types of inflammatory muscle disease. These conditions typically present with bilateral (both sides) large muscle weakness. In the case of DM, rash can be a presenting sign. Diagnosis consists of four major features, including elevation of creatine kinase (CPK), signs and symptoms such as muscle weakness, elevated muscle enzymes (creatine kinase, aldolase), electromyograph (EMG) abnormalities, and a positive muscle biopsy. Often, laboratory test abnormalities can be seen including the presence of autoantibodies such antinuclear antibody (ANA), and the myositis-associated antibodies.
In both PM and DM, inflammatory arthritis can be present and can look like RA — including lung involvement. In RA, however, unless an overlap syndrome – ie., a patient having both RA as well as muscle disease) is present, muscle function should be normal. Also, in PM and DM, erosive joint disease is unlikely. RF and anti-CCP antibodies are typically elevated in RA and not PM or DM.
Spondyloarthropathies (SA)
A group of arthritic conditions called the spondyloarthropathies which include psoriatic arthritis, reactive arthritis, ankylosing spondylitis, and enteropathic arthritis are a category of disease that cause inflammation throughout the entire body, particularly in parts of the spine and at other joints where tendons attach to bones. They also can cause pain and stiffness in the neck, upper and lower back, tendonitis, bursitis, heel pain, and fatigue. They are often called seronegative arthritis. The term ‘seronegative’ means that tests for lab markers such as rheumatoid factor are negative. Symptoms of adult SA include:
Back and/or joint pain;
Morning stiffness;
Tenderness near bones;
Sores on the skin;
Inflammation of the joints on both sides of the body;
Skin or mouth ulcers;
Rash on the bottom of the feet; and
Eye inflammation.
In some cases of SA, peripheral arthritis resembling RA can be present. Careful history and physical examination can usually distinguish between these syndromes, especially if an obvious disease that is aggravating inflammation is present (psoriasis, inflammatory bowel disease). In addition, since RA rarely affects the end joints of the fingers (DIP joints), if these joints are involved from inflammatory arthritis, the diagnosis of an SA is favored. Usually, RF and anti-CCP antibodies are negative in SA, although in some cases of psoriatic arthritis there may be elevations of RF and anti-CCP antibodies.
Crystal Associated Arthritis
Monosodium Urate Disease (Gout)
Gout is due to deposition of monosodium urate crystals in a joint. Gouty arthritis is typically sudden in onset, very painful, with signs of significant inflammation on exam (red, warm, swollen joints). Gout can affect almost any joint in the body, but typically affects “cooler” regions including the toes, feet, ankles, knees, and hands. Diagnosis is made by withdrawing fluid from a joint and examining the fluid under a polarizing microscope. Patients may also have elevated serum levels of uric acid.
In most cases, gout is an acute disease that affects one joint and is easily distinguished from RA. However, in rare cases, chronic erosive inflammation can develop and affect multiple joints. And, in cases where tophi (deposits of uric acid under the skin) are present, it can be difficult to distinguish from erosive RA. However, crystal analysis of joints or tophi and blood tests should be helpful in distinguishing gout from RA.
Calcium Pyrophosphate Deposition Disease (CPPD; Pseudogout)
CPPD disease is caused by deposits of calcium pyrophosphate dehydrate crystals in a joint. The body’s reaction to these crystals, leads to significant inflammation. Diagnosis includes:
Detailed medical history and physical exam;
Withdrawing fluid from a joint using a needle;
Joint x-rays to show crystals deposited on the cartilage (chondrocalcinosis);
Blood tests to rule out other diseases (e.g., RA or osteoarthritis).
In most cases, CPPD arthritis presents with acute arthritis affecting one or more joints. However, in some cases, CPPD disease can present with chronic symmetric multiple joint erosive arthritis similar to RA. RA and CPPD disease can usually be distinguished by joint fluid examination demonstrating calcium pyrophosphate crystals, and by blood tests, including RF and anti-CCP antibodies, which should be negative in CCPD arthritis.
Sarcoid Arthritis
Sarcoidosis is an inflammatory type of arthritis. The majority of patients with this disease have lung disease, with eye and skin disease being the next most frequent signs of disease. In most cases, the diagnosis of sarcoidosis can be made on clinical and x-ray presentation alone. Patients will have acute arthritis, painful nodules under the skin on the shins (erythema nodosum), and a chest x-ray showing enlargement of lymph niodes. In some cases, the demonstration of a specific type of inflammation change, called a noncaseating granuloma on tissue biopsy, is necessary for definitive diagnosis.
Arthritis can be present in approximately 15% of patients with sarcoidosis, and in rare cases can be the only sign of disease. In acute sarcoid arthritis, joint disease is usually rapid in onset, symmetric, involving the ankle joints. The knees, wrists, and small joints of the hands can be involved. In most cases of acute disease, lung and skin disease are also present. Chronic sarcoid arthritis typically involves one or maybe a few joints and due to its often erosive nature can be difficult to distinguish from RA.
Polymyalgia Rheumatica (PMR) / Temporal Arthritis
PMR is a form of arthritis that leads to inflammation of tendons, muscles, ligaments, and tissues around the joints. It is characterized by large muscle (shoulders, hips, thighs, neck) pain, aching, morning stiffness, fatigue, and in some cases, fever. It can be associated with temporal arthritis/giant-cell arthritis (TA/GCA) which is a related but more serious condition in which inflammation of large blood vessels can lead to complications such as blindness, aneurysms and cramping pain in the arms or legs (limb claudication) due to inflammation and narrowing of the large blood vessels in the chest and extremities. PMR is diagnosed when the clinical picture is accompanied by elevated markers of inflammation (ESR and/or CRP). If temporal arthritis is suspected (headache, vision changes, limb claudication), biopsy of a temporal artery may be necessary to make the diagnosis.
PMR and TA/GCA can present with symmetric inflammatory arthritis similar to RA. These diseases can usually be distinguished by blood tests. In addition, headaches, acute vision changes, and large muscle pain are uncommon in RA, and if these are present, PMR and/or TA/GCA should be considered.
Infectious Arthritis
Many infections can present with arthritis either due to direct joint infection or due to autoimmune joint inflammation. In most cases, infections lead to acute single joint arthritis; however, in some cases, chronic arthritis affecting a few or many joints can be present. Because missed infections can lead to significant complications, it is crucial to have a high index of suspicion for infection in any patient presenting with acute or chronic arthritis.
Lyme disease
Lyme disease is an infection due to a type of bacteria called a spirochete. The disease is manifested by a skin rash, swollen joints and flu-like symptoms, caused from the bite of an infected tick. Symptoms may include:
A skin rash, often resembling a bulls-eye (target lesion);
Fever;
Headache;
Muscle pain;
Stiff neck; and
Swelling of knees and other large joints.
The diagnosis of Lyme disease is typically made by blood testing. If, however, chronic single joint arthritis develops, joint fluid analysis or joint tissue biopsy may be necessary for diagnosis. Lyme arthritis can usually be distinguished from RA by clinical presentation and blood tests.
Acute rheumatic fever (ARF)
Acute rheumatic fever is an inflammatory disease that may develop after an infection with the Streptococcus bacteria (strep throat or scarlet fever). The disease can affect the heart, joints, skin, and brain. Symptoms include:
Fever;
Joint pain;
Arthritis (mainly in the knees, elbows, ankles, and wrists);
Joint swelling; redness or warmth;
Abdominal pain;
Skin rash
Skin nodules;
A peculiar movement disorder (Sydenham’s chorea)
Nosebleeds;
Heart problems, which can be asymptomatic.
The diagnosis of ARF is made by clinical assessment and blood testing for antibodies against streptococcal proteins. ARF and RA can have similar clinical features including arthritis and nodules. However, ARF can usually be distinguished from RA by clinical presentation. Rash and migratory arthritis are unusual in RA. The use of blood tests is also helpful.
Viral arthritis (hepatitis B and C, parvovirus, EBV, HIV)
Arthritis may be a symptom of many viral illnesses. This makes viral infections a great masquerader. The duration is usually short, and it usually disappears on its own without any lasting effects. Clinical features in adults:
Joint symptoms occur in up to 60%. These can be symmetric and affect the small joints of the hands, wrists, and ankles as well as the knees. Morning stiffness is also present.
Parvovirus B19 is a very common viral infection that looks like RA.
Diagnosis of viral arthritis is made by serologic testing. A high percentage of patients with hepatitis C may have elevated titers of RF. Therefore, RF testing is not helpful in distinguishing between hepatitis C infection and RA. However, in these situations, testing for anti-CCP can be helpful as anti-CCP antibodies have not been shown to be significantly elevated in isolated hepatitis C infections.
So as you can see… “it ain’t easy…”
Nathan Wei, MD FACP FACR is a rheumatologist and Director of the Arthritis and Osteoporosis Center of Maryland. He is a Clinical Assistant Professor of Medicine at the University of Maryland School of Medicine. For more info: Arthritis Treatment