Article Author:
Shayan Senthelal
Article Editor:
Mark Thomas
11/14/2018 9:10:56 PM
PubMed Link:


Arthritis is derived from the Greek term “disease of the joints.” It is defined as an acute or chronic joint inflammation that often co-exists with pain and structural damage. [1] Arthritis affected both the Neanderthals and ancient Egyptians, but It was not until 1886 that Dr. John K. Spencer coined the term “osteoarthritis.”

Arthritis describes a set of symptoms that includes pain, stiffness, and joint deformities subsequent to an inflammatory process. The destructive process can occur through multiple pathways. These include:

  • Degenerative disease (osteoarthritis)
  • Auto-immune or auto-inflammatory processes (rheumatoid arthritis and ankylosing spondylitis)
  • Crystal deposition (gout and pseudogout)
  • Infection (septic arthritis)
  • Idiopathic (juvenile idiopathic arthritis).

Many diseases can result in arthritis. Examples include systemic lupus erythematosus, psoriasis, Lyme disease, reactive arthritis, and celiac disease among numerous others.

The goal of this review is to provide a general overview of the most common arthritides and briefly touch on key aspects of the different major disease types.


Numerous insulting factors can perpetuate the cascade of joint destruction. Common causes of joint inflammation include the wear-and-tear associated with day-to-day weight-bearing, a prior history of trauma/ injury to the joint(s), prior infection, deposition of monosodium urate or calcium pyrophosphate dihydrate crystals, or autoimmune processes. [2]


Over one-third of the American population has arthritis on imaging, and this number is bound to increase with the mean population age. [3] Of the arthritides, osteoarthritis is most prevalent. Between 19% and 30% of adults over the age of 45 years have knee osteoarthritis[4], 27% have osteoarthritis of the hand, and 27% have osteoarthritis of the hip. [5] It is estimated that 40% of men and 47% of women will develop osteoarthritis in their lifetime, with the incidence increasing to 60% if they have a body mass index greater than 30. [6]

Rheumatoid arthritis is found in approximately 1% of Caucasians, with females being affected more frequently than males (lifetime risk of 3.6% in women vs. 1.7% in men). [7] Disease onset is typically after age 50, with a disease prevalence of 5% in women over the age of 65.

Crystal arthropathies include gout (monosodium urate crystals) and pseudogout (calcium pyrophosphate dihydrate crystals). Approximately 3% of adults suffer from gout. [8] The first metatarsophalangeal joint is most commonly involved, and 20% have a polyarticular pattern. The prevalence of pseudogout in the adult population is between 4% and 7% with over half of patients suffering from knee arthritis. [9]

Septic arthritis is typically caused by bacterial seeding of an already arthritic joint via hematogenous spread, most often from a skin or a urinary tract infection. Septic arthritis has a prevalence of 0.01% in the general population and 0.7% in patients with rheumatoid arthritis. [10]


Osteoarthritis is characterized by a degenerative cascade of progressive cartilage loss which leads to bone damage. Characteristic findings include subchondral cysts, osteophytes, and subchondral plate thickening. Interleukin-6, monokines, interferon-induced protein-10, and macrophage chemotactic protein induce proteolytic enzymes such as matrix metalloproteinases, serine proteases, and cysteine proteinases and result in the degradation of joint collage. [11] Calcification of the surrounding articular cartilage reduces the thickness of and eventually destroys the cartilaginous matrix. Old age also is associated with a decrement in chondrocyte function, enhancing susceptibility to osteoarthritic degeneration.

Symptoms of rheumatoid arthritis are typically more severe than those of osteoarthritis. Rheumatoid arthritis is a systemic and chronic inflammatory state caused by an autoimmune response to an environmental trigger. The degradation of cartilage and, eventually, bone is preceded by endothelial cell activation and synovial cell hyperplasia. The pathology occurs following the aberrant production of inflammatory mediators (such as tumor necrosis alpha, interleukins 1, 6 and 8 and others following exposure to an antigenic pathogen). [12]

The monosodium urate salts of gout precipitate as needle-shaped crystals. This crystallization is more likely to occur in cooler body parts and with acidic conditions. The process is different in pseudogout where the inorganic pyrophosphate from chondrocytes combines with calcium to form calcium pyrophosphate dihydrate. This crystal is deposited in joint spaces that have a predilection to osteoarthritic changes. Pseudogout crystal damage includes the fragmentation of bone and cartilage and the formation of osteophytes and subchondral cysts. Metabolic disorders such as hemochromatosis, hyperparathyroidism, or hypomagnesemia increase the likelihood of calcium pyrophosphate deposition. [13]

Septic arthritis is typically an inflammatory response to a monobacterial infection. Bacterial entry into the synovial fluid triggers a release of cytokines, chemokines, and proteases that degrade cartilage and trigger hyperplasia of the synovial membrane. Toxins produced by bacteria play an additional destructive role within the joint space itself. In adults, Staphylococcus aureus is the most common pathogen (with streptococci strains also being common). [14] Infection by gram-negative bacteria is more commonly seen as a result of trauma, intravenous drug use, immunosuppression, or in the elderly or very young.

History and Physical

Neurological and other musculoskeletal diseases can present in a similar fashion to the arthritides. Diagnosis must be accurate and based upon objective findings. Pain should be assessed appropriately, noting the location, character, onset, severity, and modifying factors of the symptoms. The distribution of affected joints should be assessed, and related symptoms such as stiffness, swelling, or warmth noted. The temporal and spatial pattern of symptoms, such as pain migrating from joint to joint, the symmetry of symptoms, and the progression of disease must be considered.

Prior medical history can provide insight. For example, a history of prior trauma can lead to hemarthrotic joints. Septic arthritis may include a warm and erythematous joint in the setting of constitutional symptoms (fever and chills). A fracture might increase the risk of developing osteoarthritis. The presence of high grade fever, a history of immunosuppression, and a recent history of travel all increase the likelihood of septic arthritis in contrast to a history of low grade fever which is more consistent with pseudogout or rheumatic arthritis. A history of recent sexually transmitted disease and/ or gastrointestinal symptoms might suggest a diagnosis of reactive arthritis. Extra-articular and systemic symptoms can provide clues to the underlying diagnosis.

Osteoarthritic symptoms typically improve with rest and worsen with activity. For the patient with rheumatoid arthritis, immobility worsens pain and other symptoms and results in morning stiffness. This stiffness typically improves after approximately thirty minutes of activity. [15]

The physical examination is crucial in the evaluation of the affected joint(s). The identification of effusions or synovitis suggests a rheumatoid, inflammatory, or infective arthritis. Note that while a loss of joint range of motion may be related to arthritis, it can also be due to other soft tissue disorders.

When present, nodules are helpful diagnostic findings. Rheumatoid nodules are found in rheumatoid arthritis, while tophi are characteristic of gout and erythema nodosa is found in sarcoidosis.

The presence of rash, dryness, eye findings, ulcerations of mucus membranes, Raynaud phenomenon, fatigue, or a family history of rheumatic disease increases the likelihood of rheumatic arthritis. Skin findings can be present in psoriatic arthritis and Still disease while eye involvement such as episcleritis and conjunctivitis can be found in reactive arthritis. [16]


Imaging and serology can assist in the diagnosis and grading of the severity of an arthritic condition. X-rays, ultrasound, CT, and MRI can define the underlying pathology, determine the extent of joint space destruction and reveal the stability and integrity of the surrounding joint structures. Findings may include fractures, joint space narrowing, effusions, tumors, chondrocalcinosis, osteonecrosis, and tophi. Like standard radiographs, ultrasound evaluation can identify synovitis and effusions of the joint space, but it also improves the accuracy of joint fluid aspiration or joint injection. [17] Injections can also be fluoroscopically or CT-guided. The use of MRI may assist in evaluating soft tissue or ligamentous injuries which are otherwise difficult to identify.

Examination of a synovial joint fluid sample can determine its cellular properties (i.e., red and white blood cell count, crystals, glucose content, and lactate dehydrogenase level). This can be critical in the evaluation of a potentially septic or inflammatory joint. A synovial biopsy also can be performed, particularly for suspected cases of sarcoidosis or fungal or mycobacterial infection. [18]

Additional serological markers are often considered when diagnosing the cause of arthritic joints. Tests such as pathogen cultures, inflammatory markers (ESR and CRP), antinuclear or anti-citrullinated peptide antibodies, and rheumatoid factor are important diagnostic elements. [19]

Treatment / Management

The management of osteoarthritic joints should aim to limit pain and improve function. Usually, a combination of non-pharmacological (or conservative) and pharmacological treatments are required for optimal care. Non-pharmacologic treatments include specific exercises, physical therapy, bracing, acupuncture, and weight reduction. The pharmacologic management of osteoarthritis utilizes topical and oral medications. Frequently used medications include oral and topical non-steroidal anti-inflammatory drugs (NSAIDs), topical capsaicin, and duloxetine. Corticosteroids can be injected directly into the joint.

In most instances, topical NSAIDs, capsaicin, and other ointments are first line therapy, and oral NSAIDs are to be initiated if symptoms are not relieved by these, or the disease is more systemic. Duloxetine can be useful for patients that have medical contraindications to NSAID use. If both non-pharmacological and pharmacological management fails, intra-articular corticosteroid injections might provide symptom relief. Opioids should be avoided. [20]

Surgical replacement of the affected joint(s) is reserved for refractory symptoms and can be highly effective. Patients may experience post-surgical complications and limited function in the immediate post-surgical period is not unusual. [21] Physical therapy is often necessary post-operatively to optimize patient outcomes.

The emphasis in the pharmacological management of rheumatoid arthritis and the seronegative spondyloarthropathies is on early disease mitigation. The early use of disease-modifying anti-rheumatic drugs (DMARDs) and biologics is more effective than treatment with glucocorticoids and NSAIDs. [22] Anti-inflammatories can be used as an adjunct to reduce the amount of inflammation while the disease remains active. Regular monitoring of symptoms and dose adjustment continues through symptom remission. Treatment of disease exacerbations may require corticosteroids when severe. [23]

Baseline laboratory tests should be obtained. Ophthalmologic evaluation is recommended for patients started on hydroxychloroquine. Screen for inactive tuberculosis in those started on biologic agents and for hepatitis B and C for those being started on immunosuppressive medications or DMARDs. [24]

In gouty arthritis, flare-ups can be quite debilitating and painful. The use of anti-inflammatory medications can provide substantial relief. These include oral corticosteroids (typically a prednisone taper), NSAIDs such as indomethacin or high-dose naproxen, or colchicine. The use of intra-articular corticosteroid injections may be useful for a patient with pauciarticular involvement, whereas the use of intramuscular or intravenous corticosteroids may be used for systemic symptoms. Medications that decrease uric acid levels play no beneficial role in the treatment of an acute flare. [25] 

The treatment of septic arthritis requires draining the affected joint and the use of antibiotics. Cultures and sensitivities of the joint fluid will determine which antibiotics will be effective. [26]

Pearls and Other Issues

Arthritis is a broad and complex topic with many types, subtypes, and variations. The above is a summary of this expansive subject and does not aim to cover it in its entirety. It does, however, aim to provide an introductory synopsis of the arthritides and give the reader the knowledge to diagnose and treat this condition in most settings.

Enhancing Healthcare Team Outcomes

Arthritis may be a disease of the joint but it also has systemic repercussion. The disorder can severely diminish the quality of life and lead to depression. Depending on the type of arthritis, there may also be other organs involved. The management of arthritis is ideally done by a multidisciplinary team that includes a nurse, dietitian, rheumatologist, physical therapist, orthopedic surgeon, pain specialist, pharmacist and an internist. Polypharmacy is a major concern in these patients because of the need to resolve the pain, hence the pharmacist should closely monitor the medications to prevent serious drug interactions. Almost all patients may benefit from a physical rehabilitation consult. In addition, a dietitian can help educate the patient on a healthy diet. The nurse should educate the patient on medication compliance, abstaining from alcohol and discontinuing smoking. Since arthritis is a progressive disease, all patients should be urged to have close follow up with the primary care provider. A referral to a pain consultant early in the course may help prevent abuse of narcotics and other prescription strength pain medications.