Most skeletal muscles work in groups. The prime mover is the muscle that contracts to produce the movement. Synergists are muscles that work with prime movers to assist in performing the movement. Antagonists are muscles that work opposite prime movers by relaxing during their contraction or by producing an opposite effect. For example, the arm is flexed by contracting the biceps brachia, which acts as the prime mover; at the same time, the triceps brachii on the opposite side of the humerus relaxes, acting as the antagonist (Figure 1). When the arm is extended, the roles of the biceps and triceps are reversed. An isotonic contraction occurs when a muscle shortens during contraction. An isometric contraction occurs when a muscle becomes tense while remaining the same length [2].

A bursa is a fluid-filled sac that facilitates motion of structures that move against each other. It can be found between skin and bone, muscle and bone, tendons and bone, ligaments and bone, and between muscles. The bursae function as padding between structures to reduce friction caused by moving parts [4].

Skeletal muscle contraction begins with the stimulus of a muscle fiber by a motor neuron. Every motor neuron ends in many fine branches, with each branch connecting with an individual muscle fiber. A group of muscle fibers activated by a single motor neuron is called a motor unit. Motor units range in size from a single muscle fiber in muscles controlling fine, skilled movements to over one hundred fibers in muscles involved in gross movements. All the fibers of a motor unit contract together when the neuron is stimulated [6]. There are two types of motor units in skeletal muscle, Type 1 and Type 2. Type 1 has a small cell diameter, with a high excitability and fast conduction velocity. It has an oxidative profile with moderate contraction velocity and low fatigability. There are few muscle fibers of this type. In contrast, Type 2 has a large cell diameter, with low excitability but a very fast conduction velocity. Type 2 fibers are numerous in quantity, with a glycolytic profile and high fatigability. The small motor units, with Type 1 (also known as "slow-twitch") fibers, are recruited first and are frequently active, while the large motor units, with Type 2 ("fast-twitch") fibers, are used infrequently, in forceful contractions. Maximal efforts, in which fast motor units are recruited, cannot be sustained because of the rapid depletion of glycogen.

The joint is the musculoskeletal structure most frequently influenced by degenerative disease. Changes are most often associated with aging, excess weight, trauma, and inflammatory conditions. In the presence of these factors, articular cartilage softens, thins, and ulcerates, and the joint surfaces become rough. There may be a narrowing of the joint space and swelling of adjacent soft tissue. The normal smooth-gliding joint action is diminished, and the periosteum becomes irritated by friction, stimulating the growth of bone spurs at the joint margins. The effects of this destruction include joint pain, stiffness, and joint deformity, which can result in slight to moderate limitation of movement. Crunching or grating sounds, called crepitus, may be heard upon movement [8,9].

Joints may be assessed for changes by observation and palpation. Heberden nodes may be noted on the distal interphalangeal joint of patients with osteoarthritis. Likewise, rheumatoid nodules may be noted near the joints of patients with rheumatoid arthritis, even in the absence of other signs. Joints may be compared bilaterally to assess symmetry, position, and changes in alignment [17,19].

Range of motion can be measured with an instrument called a goniometer. Placing the arms of the goniometer parallel to the axis of the bones that form the joint, the examiner measures the angle for the typical positions of the joint. The elbow's normal flexion, for example, is 160^o, whereas its normal extension is 0^o. To determine what is normal for a patient, compare a joint with an apparently impaired range of motion to the corresponding joint in the other extremity, if possible. Patients can have differences in range of motion for a variety of reasons, particularly as they age, so it is vital to assess typical range of motion on an individualized basis. Dexterity is usually assessed by asking the patient to pick up an object from a flat surface [17,18].

The antinuclear antibody (ANA) test is the most specific and sensitive test for lupus and is therefore the most commonly used autoantibody test. Ninety-seven percent of patients with lupus have a positive ANA blood test. The titer and patterns of the blood sample are reported. A titer greater than 1:80 is usually considered positive [21]. It is important to note that a positive ANA test is found in 97% of patients with lupus, but alone, it does not indicate a conclusive diagnosis of lupus [21]. A positive ANA test, although not always found, satisfies one of the four typical clinical characterizations required for a definitive diagnosis of lupus. ANA tests may also be positive in patients with other connective tissue diseases, chronic infectious diseases, and autoimmune diseases [21].

Because it is readily available and avoids the use of radiation, ultrasonography is often a good option in the assessment of musculoskeletal disorders and injuries. Ultrasound allows for the visualization of joints, tendons, muscles, bursae, ligaments, cartilage, nerves, fascia, and related soft tissue and can have a role in diagnosis and/or evaluation of disease progression for a variety of conditions. The American Academy of Physical Medicine and Rehabilitation indicates that ultrasound is an essential component in the diagnosis of tendinopathies/tendon tears, nerve entrapments (e.g., carpal tunnel syndrome), and acute or chronic muscle injury [32]. It may also be involved in the evaluation of ligamentous injury and joint instability syndromes, subluxations/dislocations, and fascia injury or inflammation. When joint aspiration is necessary, it may be guided by ultrasound, as may therapeutic injections.

There is wide variability in clinical symptoms in Marfan syndrome, with the most notable occurring in eye, skeleton, connective tissue, and cardiovascular systems. The most common symptom is myopia. Ocular problems are a result of defective supporting tissue of the lens, which can cause bilateral subluxation or total dislocation of the lens. The dislocation is usually upward, but slit-lamp examination is done to detect more subtle variations. Complications such as reduced visual acuity, uveitis, glaucoma, cataracts, and retinal detachment may also occur [33].

The patient may have episodes of bleeding, including spontaneous epistaxis; bleeding into the joints (hemarthrosis); blood in the sputum (hemoptysis); dark, tarry stools (melena) indicating bleeding in the digestive tract; and bleeding gums. It is not known whether the abnormal bleeding is from weakness in blood vessel walls or abnormal interactions of platelets with collagen [33]. Patients with Ehlers-Danlos syndrome who become pregnant are at risk for uterine rupture.

The major symptom of bursitis/tendinitis/tendinosis is pain, often so severe that the patient is unwilling to move the affected part. Swelling may be present, and this alone may keep the patient from moving the joint. Any of the body's many bursae and tendons can become inflamed, but some joint areas are more commonly affected than others. Differential diagnosis of acute pain and erythema in joint areas should include infection, gout, and rheumatoid arthritis [37].

The measures employed for relief of bursitis and tendinitis vary according to the patient's age and the location, cause, and severity of the injuries. Recommendations usually include [37]:

Polymyalgia rheumatica is an immune-mediated inflammatory disorder characterized by muscle stiffness, pain, and weakness around the neck, shoulders, and hip. While this is an inflammatory disorder, the cause of trigger is unclear; genetic, infectious (e.g., Epstein-Barr virus, parvovirus), and gut health-related etiologies have all been suggested, with varying levels of evidence [43]. The incidence increases with age, with the greatest incidence in White patients older than 50 years of age; the average age at diagnosis is 70 years.

Four different forms of lupus have been identified: cutaneous lupus erythematosus, drug-induced lupus, neonatal lupus, and systemic lupus erythematosus (SLE) [47]. Cutaneous lupus mainly affects the skin. It is associated with chronic skin eruptions that, if left untreated, can lead to scarring and permanent disfigurement. Drug-induced lupus is associated with ingestion of various drugs that result in lupus-like symptoms. Neonatal lupus is a rare, non-systemic condition affecting infants of women with lupus. SLE, which affects multiple organ systems as well as the skin, is considered the most common of the four forms.

Immune dysregulation, in the form of autoimmunity, is thought to be the prime cause of lupus. In patients with lupus, the body produces an accelerated inflammatory response, resulting in the production of autoantibodies, causing immune complexes (antigens combined with antibodies) [49,56]. These autoantibodies and complexes assault the body's own healthy cells and tissues [47,49,50,51]. Symptoms of SLE are the result of the damage to the body's tissues secondary to the immunologic response. One of the hallmark indicators of lupus is the formation of autoantibodies, and the presence of autoantibodies in the blood is a key factor to the diagnosis of lupus [47,49,51].

Common symptoms of lupus include fever, weight loss, malaise, fatigue, skin rashes, polyarthralgia, vasculitis, Raynaud syndrome (discussed in detail later in this course), patchy alopecia (hair loss), and painless ulcers of the mucous membranes [51]. Fatigue is probably the most universal symptom, described as a persistent complaint of a paralyzing fatigue that normal rest may not relieve [47]. Vague symptoms of lupus include aching, fatigue, low-grade or spiking fever, chills, and malaise. Episodic fever is reported by more than 80% of all patients with lupus, with a low-grade fever most often noted [47]. Infection is certainly a major concern and is a potential symptom for patients with lupus. Those with lupus are more susceptible to opportunistic infections due to alterations in their hematologic system, especially in white blood cells. Women with lupus may also experience irregular periods or amenorrhea due to the disease process [47,49].

Although there is no cure for lupus, there are several types of drugs available to aid in the treatment and management of secondary symptoms. Among these drug classes are nonsteroidal anti-inflammatory drugs (NSAIDs), corticosteroids, antimalarials, biologics, and immunosuppressives. In cases of severe lupus kidney disease not helped by pharmacologic intervention, dialysis or kidney transplant may be necessary.

The most frequent presentation in systemic scleroderma is the clinical triad of skin changes, Raynaud phenomenon, and esophageal hypomotility. However, manifestations are often present in other organ systems, requiring continual monitoring [46].

Intravenous iloprost is also recommended for patients with systemic scleroderma who experience digital ulcers [69]. PDE-5 inhibitors have been proven to expedite healing and prevent the development of digital ulcers and should be considered for these patients. Patients who do not respond to calcium channel blockers, PDE-5 inhibitors, or iloprost therapy, may be prescribed bosentan, which has been shown to reduce the number of new digital ulcers in patients with systemic scleroderma. Physical therapy for the hands is important to prevent contractures. For patients with Raynaud phenomenon, biofeedback is sometimes useful for controlling temperature in the hands and feet [46].

A sprain is an injury to a ligament caused by forcing a joint beyond its normal range of motion. The ligament may be stretched or actually torn. Sprains usually occur following a blunt blow during sports activities or falls. A strain is an injury to a muscle and/or tendon at any location from origin to insertion.

The most common sprains affect the ankle and occur when inversion of the foot tears a ligament, usually the anterior talofibular ligament. Knee sprains cause swelling, hemarthrosis, significant decrease in range of motion, and joint laxity. Often the person hears a "pop" when the injury occurs and later describes the knee as feeling as it is going to "give way." The medial collateral ligament is most commonly involved [70]. Following the acute injury, patients are usually able to bear weight.

Treatment of rhabdomyolysis focuses mainly on prevention of kidney damage and acute renal failure. Therefore, fluid therapy to increase urine output (and dilute urine) is the standard of care. The American Society of Nephrology has identified an ideal fluid regimen for these patients consisting of half isotonic saline (0.45%, or 77 mmol/L sodium), to which 75 mmol/L sodium bicarbonate is added [74]. At least 3–6 L should be administered per 24 hours; however, up to 10 L (or more) may be given if continuous supervision is possible. If necessary, 10 mL/hour of mannitol 15% may be added to further increase urine output. In cases that have already progressed to overt renal failure, extracorporeal blood purification is warranted [74].

The manifestations of psoriatic arthritis vary from patient to patient. Some have distal joint involvement, while others have widespread deformity, ankyloses, and joint destruction. The disease can be symmetrical or asymmetrical, and some patients have spondylitis, sacroiliitis, eye problems, or a combination. Nodules are not present with psoriatic arthritis [76].

Urate-lowering therapy should be initiated in all patients with tophaceous gout, radiographic damage due to gout, or frequent gout flares [88]. Therapy should be started within 24 to 36 hours of the onset of an acute gout attack unless otherwise contraindicated. Urate-lowering therapy is not recommended for patients experiencing their first flare, or for patients with asymptomatic hyperuricemia (serum urate >6.8 mg/dL) with no prior gout flares or subcutaneous tophi [88]. Allopurinol (≤100 mg/day) is the preferred first-line agent. Febuxostat (≤40 mg/day) is an acceptable alternative [88]. Probenecid may be used as an alternative to allopurinol or febuxostat if there is contraindication or intolerance to these preferred agents. However, probenecid should be avoided in patients with a history of urolithiasis [83,87,88].

Risk factors for developing low back pain can be generally categorized as nonmodifiable, such as old age, female sex, poverty, and lower education level, and modifiable, including higher body mass index (BMI), smoking, lower perceived general health status, physical activity (e.g., bending, lifting, twisting), repetitive tasks, job dissatisfaction, and depression. The greatest contributors to low back pain episodes are single-event or repetitive exposures to mechanical stress and age-related degenerative spinal changes. With chronic low back pain, mechanical and biophysiologic factors play a minimal secondary role to the primary contribution from psychosocial factors [91].

Nonspecific Low Back Pain. Up to 85% of low back pain in patients presenting to the primary care setting is nonspecific, meaning that it lacks a clear origin and is not caused by specific local or systemic disease or spinal abnormality [93]. Nonspecific low back pain is a diagnosis of exclusion made after ruling out serious causes of the back pain. Although pain can originate from ligaments, facet joints, muscle, fascia, nerve roots, the vertebral periosteum, or outer portions of the disk, the effective management of nonspecific low back pain does not require a precise anatomic diagnosis [94]. The pain is usually unilateral and may radiate to the buttocks or posterior thigh but not past the knee. This can lead to incorrect diagnosis of radiculopathy or disk herniation. However, true radicular symptoms radiate below the knee in a dermatomal distribution and can involve sensory loss, weakness, or reflex changes. Painful spasm may be present, and pain may be worsened by movement, while lying flat decreases the pain. Complaints of numbness, weakness, or bowel or bladder dysfunction are absent [95]. Degenerative changes revealed by lumbar imaging should usually be considered nonspecific, because they poorly correlate with symptom severity [96].

Sacroiliac Joint Syndrome. SI joint syndrome typically manifests as localized pain in the lower back or upper buttock area that overlies the SI joint. Pain is intensified by attempts to walk up stairs, and while pain may be referred to the posterior thigh, extension below the knee is unusual [100]. Tenderness over the SI joint is often found in physical examination, and pain is aggravated by the Patrick test or single-leg standing [97]. The onset of SI joint pain is usually gradual (over months to years), and although etiology is often elusive, trauma, infection, and tumor represent infrequent yet known causes of SI joint pain [100].

The proper assessment of the patient with back pain requires vigilance and careful attention for factors and warning signs suggestive of serious or life-threatening disorders. A thorough history and physical examination should be performed on all patients, during which the patient is assessed for the presence of warning signs or ''red flags." Red flags represent alarm symptoms or signs that warrant prompt, specific diagnostic testing, urgent treatment, or referral to a specialist. Among these are weight loss, prior history of cancer, nocturnal or rest pain, age older than 50 years, recent trauma, fever and chills, history of injection drug use, chronic corticosteroid therapy, difficulty urinating, bowel or bladder incontinence, and neurologic deficits such as saddle anesthesia, perianal or perineal sensory loss, or motor weakness in the extremities [93,95,101]. As an example, there is a common association between spontaneous vertebral fracture and any combination of age older than 70 years, female gender, recent trauma, and prolonged corticosteroid use. There is also a moderate to highly significant predictive value for age older than 50 years, history of prior cancer, unexplained weight loss, and failure of conservative therapy in identifying spinal malignancy [101].

Although acute low back pain improves in most patients within three to six weeks using conservative therapy, up to 33% of patients with low back pain report pain of moderate or greater severity at one-year follow-up and 20% report ongoing pain severe enough to limit activity [96]. With chronicity, low back pain may become disabling and impose a severe emotional and functional burden. The management goals for chronic low back pain are to minimize pain and disability, improve functional status, and facilitate restoration of normal activity, while limiting the use of marginally effective or inappropriate medication [93].

Scoliosis is a lateral curvature of the spine, most commonly in the thoracic area with convexity to the right and compensatory convex curve to the left in the cervical and lumbar areas. Scoliosis can be functional (a result of poor posture or leg-length discrepancy) or structural (a result of deformity of the vertebral bodies, paralysis, congenital malformations, or idiopathic causes). Idiopathic causes are the most common and appear with increased growth during adolescence. It disproportionately affects girls, who are 10 times more likely to be diagnosed than boys at 10 years of age or older [108].

Carpal tunnel syndrome is generally associated with such umbrella terms as repetitive stress injuries, work-related upper extremity disorders, musculoskeletal disorders, entrapment neuropathies, and cumulative trauma disorders [110,111]. Specifically, carpal tunnel syndrome is a painful disorder of the wrist and hand that occurs when the median nerve (which runs from the hand to the forearm) becomes compressed [112,113].

Splinting has been found to improve patient satisfaction, symptoms, and function when measured at intervals of 2, 4, and 12 weeks. The American Academy of Orthopaedic Surgeons suggests that splinting be considered before surgery. This may be particularly helpful when weighing the risks of surgery versus the benefits. Splinting is not recommended for use after routine carpal tunnel release surgery. The benefit of splinting for postoperative rehabilitation is undetermined [126,127,128].

The primary symptom of osteoarthritis of the knee is pain, especially with weight-bearing exercise or activity, that improves with rest. Stiffness in the joint occurs in the morning, lasting 30 minutes or less, and may occur after periods of inactivity [154]. The clinical presentation of hip osteoarthritis is similar to that of knee osteoarthritis, with pain being the most common symptom driving individuals to seek medical care [155]. Pain related to hip osteoarthritis is an ache—most often diffuse—that is usually felt during use of the joint and relieved by rest. Pain is typically gradual, variable, or intermittent; the joint may feel stiff after a period of inactivity [155]. The loss of function or mobility is usually related to the degree of pain.

Rheumatoid arthritis is defined as a chronic inflammatory disease characterized by uncontrolled proliferation of synovial tissue and a wide array of multisystem comorbidities [24]. In its most common presentation, rheumatoid arthritis affects the joints, causing inflammation of the synovium and cartilage and bone loss. The precise etiology of rheumatoid arthritis is presently unknown [26]. Most likely it has an autoimmune origin (whereby an individual's immune system confuses healthy synovial tissue for foreign substances, thereby attacking the synovial joint surfaces) given that autoantibodies (e.g., rheumatoid factor, ACPA) are present and often precede the clinical manifestation of rheumatoid arthritis by many years [22,25,168].

The course and severity of the illness can vary considerably, and infection, genetic factors, and hormones may contribute to the disease. Rheumatoid arthritis appears to require the complex interaction of genetic and environmental factors with the immune system and ultimately in the synovial tissues throughout the body. Triggers for rheumatoid arthritis have long been the target of active research. Purported triggers have included bacteria (Mycobacterium, Streptococcus, Mycoplasma, Escherichia coli, Helicobacter pylori), viruses (rubella, Epstein-Barr virus, parvovirus), and superantigens [25,26,27].

Although rheumatoid arthritis has a clear genetic component, only about 1 in 25 White individuals with the so-called shared epitope develop rheumatoid arthritis [27]. Even if one monozygotic twin has rheumatoid arthritis, there is only approximately a one in six chance that the other twin will develop the same disease. Thus, other factors in addition to genetics are active as precipitators or triggers of rheumatoid arthritis [27].

A number of different medical conditions may be considered in the differential diagnosis of rheumatoid arthritis [181,186,187,188]. These include:

Rheumatoid arthritis has no known prevention or cure. Lifelong treatment is usually required, including medication, physical therapy, exercise, and possibly surgery. In order to provide the best outcomes, patients should be educated regarding the most appropriate treatment regimens for their disease manifestations, as earlier rheumatoid arthritis diagnosis can assist in aggressive early treatment for rheumatoid arthritis (when indicated), thereby delaying joint destruction. The 2010 ACR/EULAR Classification Criteria for Rheumatoid Arthritis is now a well-established diagnostic and prognostic tool; as such, guidelines (e.g., the 2016 update of the EULAR Recommendations for the Management of Rheumatoid Arthritis with Synthetic and Biological Disease-Modifying Antirheumatic Drugs) recommend that patients start treatment with a disease-modifying antirheumatic drug (DMARD) immediately following a rheumatoid arthritis diagnosis [189]. Therapeutic goals include preservation of function and quality of life, minimization of pain and inflammation, joint protection, and control of systemic complications, with the ultimate aim being low disease activity or remission [23,24,27,189,190].

The patient history is key to diagnosis, and nurses should be careful to obtain a complete and accurate history. This should include any recent viral (e.g., parvovirus, alphavirus, hepatitis, Epstein-Barr virus) and bacterial (e.g., Streptococcus pneumoniae) infection. In young, sexually active patients, the most common causative pathogen is Neisseria gonorrhea. For patients who develop infectious arthritis following trauma, puncture wounds, or injection drug use, Pseudomonas aeruginosa is the most likely cause [18,197].

Hemangiomas are rare vascular tumors often associated with arteriovenous malformations of skin vascular disease. They tend to affect younger individuals, often teenage girls who have been symptomatic since childhood. The knee is the most commonly involved joint [37].

Though it is the most common primary tumor of the joint, synovial sarcoma is rare. This malignancy can appear at any age, although it seems to predominate in young adults. The growth generally appears on a lower extremity, but synovial sarcomas can also develop in an upper extremity, the neck, or the chest [198].

Patients with synovial sarcoma often present with a slow-growing mass that may have been present for months to years, depending on how deeply seated it is in tissue. Pain may be present, or the patient may have a vague sensation of discomfort over the involved area. There may also be localized swelling. In cases involving the neck, tumor invasion may produce hoarseness, dysphagia, or dyspnea [198].

As with most cancer, survival time is dependent on the size of the tumor, site in the body, and age at diagnosis. The five-year survival rate is approximately 60%; this increases to 75% in patients 30 years of age or younger. If the tumor is in an extremity, five-year survival is about 65%; if the tumor is present in the trunk, the rate decreases to 40% [199].

Joint effusions can occur as a result of simple trauma or secondary to fractures, internal derangements, or severe sprains. Within 24 hours after a blow to the joint, synovial fluid accumulates. If blood vessels in the synovium are broken, hemarthrosis also occurs. The knee is most commonly affected by this injury, although it can occur in other joints as well [75].

In simple cases of traumatic synovitis, joint swelling with mild pain occurs. Aspiration of the joint produces clear fluid with elevated protein content and decreased viscosity. Hemarthrosis, which usually develops within 15 minutes to 2 hours after the trauma, is usually more painful than clear effusion and is accompanied by low-grade fever. Diagnosis of traumatic synovitis is primarily by physical examination, but x-ray examination is done to rule out fracture [75].