Orthopedics

Osteoarthritis (OA) is one of the most common diseases affecting the general population and is characterized by progressive, noninflammatory degenerative changes primarily involving the hips, knees, spine, hands, and feet. Among veterans the incidence and prevalence of OA is considerably higher than the incidence found in the general population. A study examining active-duty service members between 1999 and 2008 reported a 19-fold higher incidence in service members aged > 40 years compared with those aged < 20 years.1 In addition, women and African American service members seem to have a higher incidence of OA compared with other populations. Overall, the economic burden of OA is estimated to approach or exceed $60 billion annually and will continue to increase due to longer life expectancies in veterans.^2,3 Much of this burden relates to a lack of disease-modifying treatment and inadequacy of analgesic therapy.

Patterns of Osteoarthritis

The strongest risk factor associated with OA is age. Osteoarthritis is the most common cause of pain and disability in the elderly population.⁴ A heritable component seems to be associated with primary OA as shown by family risk studies.⁵ Estrogenic effects seem to protect younger women, whereas postmenopausal women are at greater risk after age 50 years. Previous joint trauma and activities have a large impact on the risk of developing OA later, particularly those activities and occupations requiring high-impact joint loading, such as those often seen in veterans. Other modifiable risk factors include smoking and obesity. The risk for knee OA has been found to increase 30-fold in patients with a body mass index > 30.⁶

Several OA disease patterns exist. The disorder can be characterized as primary or secondary. Primary OA classically presents in the aging male or postmenopausal female involving the apophyseal joints of the lumbar and cervical spine; base of the thumb (first carpometacarpal,[CMC] joint); proximal or distal interphalangeal joints (PIPs and DIPs) of the hand, knee, or hip; or the first metatarsophalangeal joint. The disease may be localized to 1 joint (localized OA) or involve multiple joints (generalized OA). The disease is more common in men aged < 45 years and more common in women aged > 45 years. In either sex, progression with age is a prominent feature.

Rarely, patients may present with inflammatory arthritis in a distribution typical of OA that is not associated with psoriasis or another disease. This form is known as inflammatory or erosive OA. A minority of cases present with rapidly progressive hip or knee degeneration, the cause of which is unknown. Osteoarthritis involving the metacarpophalangeal joints (MCPs), wrists, elbows, shoulders, or ankles is much less common. Patients with radiographic evidence of OA at these sites should be evaluated for a cause of secondary OA.

Patients often develop secondary OA in the setting of inflammatory arthritis, crystal-induced arthritis, and other systemic diseases. Causes of secondary OA should be considered when OA manifests in an atypical joint. Common causes of secondary OA are outlined in Table 1. A careful history may undercover a prior diagnosis of gout, calcium pyrophosphate deposition disease, or infectious arthritis in the affected joint. An important metabolic cause of secondary OA is hemochromatosis, which can lead to osteophytic change primarily in the second and third MCPs. Patients with diabetes mellitus-associated neuropathy may develop destructive changes in the foot (Charcot joint).

Symptoms and Examination

Osteoarthritis encompasses a wide spectrum of common conditions with similar pathophysiology. Most of these conditions share similar historic features, including pain during or after use and stiffness after prolonged periods of inactivity. Other common symptoms include swelling, joint locking or “cracking,” instability, and joint fatigue. Patients may perceive OA discomfort in different ways. Whereas one patient with knee OA may describe a sharp, gnawing pain, another may experience painless swelling and instability. Although OA is mainly considered a localized disease, patients may present with multiple areas of pain, suggesting a more generalized pattern. Patients with OA may have short periods of morning stiffness and “gelling,” but prolonged stiffness suggests the presence of inflammatory arthritis.

Examination of the osteoarthritic joint is performed with thorough palpation and range of motion testing. Evidence of joint swelling may be present near the joint line with pain on palpation. Palpable crepitus is commonly noted with restricted range of motion, usually inducing pain at the maximal range. Osteophytes or chondrophytes at the joint line may be tender and are commonly mistaken for joint swelling. In the hands, bony hypertrophy of the PIP and DIP joints may be noted (Bouchard’s and Heberden’s nodes, respectively). Pain at the base of the thumb is a common complaint in patients with OA of the CMC joint.

Most cases of OA can be diagnosed by taking a history and a physical examination without further investigation; however, plain radiographs are frequently obtained to confirm the diagnosis. Joint inflammation, when present, is usually mild. Occasionally, patients may present with evidence of warmth, effusion, and severe pain with restriction of motion. Patients with these symptoms should undergo prompt arthrocentesis to rule out infection, crystal-associated arthritis, hemarthrosis, or other inflammatory causes.

Radiographic Features

Plain radiographs are extremely helpful in denoting the extent of OA in a particular joint. Radiographic features of OA include narrowing of the joint space, osteophyte formation, and subchondral bone abnormalities. Narrowing of the joint space and alignment abnormalities occur due to loss of articular cartilage. Changes in the subchondral bone include sclerosis and cystic lesions. Erosive changes, ankylosis, and calcification of the articular cartilage are typically absent.

In the hands, a particular pattern is noted involving the PIP and DIP joints with characteristic sparing of the MCPs (Figure 1A). The first CMC joint is also commonly involved, with bony osteophyte formation and joint space loss. In the knee and hip, loss of joint space with subchondral bone cyst and osteophyte formation is common (Figure 1B).

The cervical and/or lumbar spine may reveal spondylosis, disc space narrowing, and osteophytes. More than 50% of people aged > 65 years have radiologic evidence of OA. However, radiographic evidence of OA is at least twice as common as symptomatic OA, warranting careful consideration when contemplating treatment.⁷

Pathogenesis

Normal articular cartilage is a complex tissue composed of extracellular matrix and chondrocytes. Under ideal conditions, hemostasis is maintained with balance between degradation and synthesis of extracellular matrix proteins. In the aging cartilage, a reduction of total proteoglycan synthesis occurs, decreasing its capacity to retain water. Matrix proteins are modified, leading to the accumulation of advanced glycation end products (AGEs). This process is irreversible, and AGEs cannot be removed from the articular cartilage. Chondrocytes respond to AGEs with increased catabolic activity and cytokine release. Initial chondral edema and matrix degradation leads to stress fractures in the collagen network and fissuring of the cartilage. Eventually, the microfractures lead to fragmenting of the cartilage, formation of loose bodies, and synovial inflammation. Sclerosis occurs in the subchondral bone, with accelerated bone turnover leading to osteophyte formation.⁸

Treatment

Unfortunately, no pharmacologic or nonpharmacologic therapy has been shown to reverse or halt the progression of OA. A comprehensive approach to the treatment of patients with OA is imperative for reducing disability and improving quality of life. Several sources have published guidelines for the management of OA.^9-11 More recently, comprehensive clinical practice guidelines have been published regarding nonsurgical management of hip and knee OA in the veteran population.¹²

Initially, a conservative approach is generally recommended with reduction of modifiable risk factors and patient education. Weight loss, aerobic conditioning, and physical therapy can improve function and stability. Notably, a weight reduction of 5% has been associated with an 18% to 24% improvement in knee OA.⁶ A supervised walking exercise program can be extremely beneficial for patients, with several studies showing improvement in pain, ambulatory function, and psychological well-being. Bracing devices and orthotic footwear can be helpful for compartmental unloading of the knee. The use of ambulatory assist devices (eg, canes, walkers) and splinting may also be of benefit. Topical lidocaine, capsaicin, and topical nonsteroidal anti-inflammatory drugs (NSAIDs) therapy can be useful adjuncts.

Medications are used mainly to provide analgesia and improve function while causing the fewest adverse effects (AEs) (Table 2). Contrary to conventional teaching, acetaminophen may not be as effective in the treatment of OA as previously thought. A recently published metaanalysis comparing treatments for knee OA revealed acetaminophen to be the least effective agent.¹³ Another meta-analysis showed that acetaminophen provided clinically insignificant pain relief in OA of the hip and knee.¹⁴ However, acetaminophen may be useful in the treatment of mild OA or in patients with contraindications to other oral therapies. Nonsteroidal anti-inflammatory drug therapy is more effective in a patient with inflammatory OA symptoms (eg, effusion, erosive OA) and can be added to acetaminophen if ineffective alone. Gastrointestinal protection against ulceration may be warranted, and use of NSAIDs may be contraindicated in the patient with high bleeding risk, renal insufficiency, or cardiovascular disease. In patients with low cardiac risk, celecoxib can be effective. Patients who have a contraindication to NSAIDs may find benefit from other analgesic agents, such as tramadol or duloxetine. Intra-articular corticosteroid injections can be particularly helpful for patients with a single osteoarthritic joint that has been unresponsive to oral or topical analgesics. Opioid analgesics may be used as a last resort when all other agents and therapies have failed. Most patients who require opioid therapy are awaiting surgical repair or are not surgical candidates.

Use of nutritional supplements such as glucosamine and chondroitin sulfate in the treatment of primary knee OA is controversial. These agents are not regulated by the FDA and their potency, purity, and safety are not guaranteed. Furthermore, the bioavailability of oral glucosamine and chondroitin sulfate is particularly poor, and studies have revealed conflicting evidence on their ability to reduce pain in patients with OA. Nonetheless, some evidence exists for cartilage proteoglycan integration and synthesis with glucosamine and chondroitin compounds. Most patients taking these supplements experience few AEs, and some report good responses to therapy. Some patients allergic to shellfish may experience a reaction to glucosamine products.

Hyaluronate injections can be recommended for patients with moderate OA who have failed standard medical treatment. Most clinical trials of hyaluronate suggest an analgesic benefit comparable with NSAID therapy and corticosteroid injections, but high-quality studies are lacking.

Colchicine may be effective in patients with inflammatory or noninflammatory OA. Two small studies showed colchicine to be beneficial in the treatment of primary OA of the knee.^15,16 Hydroxychloroquine may be helpful in the treatment of inflammatory OA.

Loss of joint function or severe pain refractory to medical treatment in a patient with OA likely requires surgical intervention. Patients who have difficulty ambulating more than a reasonable distance (ie, 1 block) or cannot stand in place for more than several minutes due to severe pain should be considered for total joint replacement. Patients often report awaking with severe pain at night or pain that significantly impedes their activities of daily living. In these patients, total joint replacement can be extremely beneficial and life altering.

Conclusion

Osteoarthritis is the most common arthritic disease and has a very high prevalence in the veteran population. Aging, obesity, prior trauma, and activity level are the common risk factors for the development of OA. Patterns of disease are recognizable by history, examination, and prominent radiographic features. Causes of secondary OA are important to recognize and treat. The pathogenesis of OA involves a disrupted homeostatic process leading to cartilage degradation, microfracture, subchondral sclerosis, and osteophyte formation. Treatment is unique to the individual and should include a comprehensive strategy involving patient education, exercise or physical therapy, and analgesia. Patients with severe osteoarthritis that significantly impacts activities of daily living may benefit from surgery.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Osteoarthritis (OA) is one of the most common diseases affecting the general population and is characterized by progressive, noninflammatory degenerative changes primarily involving the hips, knees, spine, hands, and feet. Among veterans the incidence and prevalence of OA is considerably higher than the incidence found in the general population. A study examining active-duty service members between 1999 and 2008 reported a 19-fold higher incidence in service members aged > 40 years compared with those aged < 20 years.1 In addition, women and African American service members seem to have a higher incidence of OA compared with other populations. Overall, the economic burden of OA is estimated to approach or exceed $60 billion annually and will continue to increase due to longer life expectancies in veterans.^2,3 Much of this burden relates to a lack of disease-modifying treatment and inadequacy of analgesic therapy.

Patterns of Osteoarthritis

The strongest risk factor associated with OA is age. Osteoarthritis is the most common cause of pain and disability in the elderly population.⁴ A heritable component seems to be associated with primary OA as shown by family risk studies.⁵ Estrogenic effects seem to protect younger women, whereas postmenopausal women are at greater risk after age 50 years. Previous joint trauma and activities have a large impact on the risk of developing OA later, particularly those activities and occupations requiring high-impact joint loading, such as those often seen in veterans. Other modifiable risk factors include smoking and obesity. The risk for knee OA has been found to increase 30-fold in patients with a body mass index > 30.⁶

Several OA disease patterns exist. The disorder can be characterized as primary or secondary. Primary OA classically presents in the aging male or postmenopausal female involving the apophyseal joints of the lumbar and cervical spine; base of the thumb (first carpometacarpal,[CMC] joint); proximal or distal interphalangeal joints (PIPs and DIPs) of the hand, knee, or hip; or the first metatarsophalangeal joint. The disease may be localized to 1 joint (localized OA) or involve multiple joints (generalized OA). The disease is more common in men aged < 45 years and more common in women aged > 45 years. In either sex, progression with age is a prominent feature.

Rarely, patients may present with inflammatory arthritis in a distribution typical of OA that is not associated with psoriasis or another disease. This form is known as inflammatory or erosive OA. A minority of cases present with rapidly progressive hip or knee degeneration, the cause of which is unknown. Osteoarthritis involving the metacarpophalangeal joints (MCPs), wrists, elbows, shoulders, or ankles is much less common. Patients with radiographic evidence of OA at these sites should be evaluated for a cause of secondary OA.

Patients often develop secondary OA in the setting of inflammatory arthritis, crystal-induced arthritis, and other systemic diseases. Causes of secondary OA should be considered when OA manifests in an atypical joint. Common causes of secondary OA are outlined in Table 1. A careful history may undercover a prior diagnosis of gout, calcium pyrophosphate deposition disease, or infectious arthritis in the affected joint. An important metabolic cause of secondary OA is hemochromatosis, which can lead to osteophytic change primarily in the second and third MCPs. Patients with diabetes mellitus-associated neuropathy may develop destructive changes in the foot (Charcot joint).

Symptoms and Examination

Osteoarthritis encompasses a wide spectrum of common conditions with similar pathophysiology. Most of these conditions share similar historic features, including pain during or after use and stiffness after prolonged periods of inactivity. Other common symptoms include swelling, joint locking or “cracking,” instability, and joint fatigue. Patients may perceive OA discomfort in different ways. Whereas one patient with knee OA may describe a sharp, gnawing pain, another may experience painless swelling and instability. Although OA is mainly considered a localized disease, patients may present with multiple areas of pain, suggesting a more generalized pattern. Patients with OA may have short periods of morning stiffness and “gelling,” but prolonged stiffness suggests the presence of inflammatory arthritis.

Examination of the osteoarthritic joint is performed with thorough palpation and range of motion testing. Evidence of joint swelling may be present near the joint line with pain on palpation. Palpable crepitus is commonly noted with restricted range of motion, usually inducing pain at the maximal range. Osteophytes or chondrophytes at the joint line may be tender and are commonly mistaken for joint swelling. In the hands, bony hypertrophy of the PIP and DIP joints may be noted (Bouchard’s and Heberden’s nodes, respectively). Pain at the base of the thumb is a common complaint in patients with OA of the CMC joint.

Most cases of OA can be diagnosed by taking a history and a physical examination without further investigation; however, plain radiographs are frequently obtained to confirm the diagnosis. Joint inflammation, when present, is usually mild. Occasionally, patients may present with evidence of warmth, effusion, and severe pain with restriction of motion. Patients with these symptoms should undergo prompt arthrocentesis to rule out infection, crystal-associated arthritis, hemarthrosis, or other inflammatory causes.

Radiographic Features

Plain radiographs are extremely helpful in denoting the extent of OA in a particular joint. Radiographic features of OA include narrowing of the joint space, osteophyte formation, and subchondral bone abnormalities. Narrowing of the joint space and alignment abnormalities occur due to loss of articular cartilage. Changes in the subchondral bone include sclerosis and cystic lesions. Erosive changes, ankylosis, and calcification of the articular cartilage are typically absent.

In the hands, a particular pattern is noted involving the PIP and DIP joints with characteristic sparing of the MCPs (Figure 1A). The first CMC joint is also commonly involved, with bony osteophyte formation and joint space loss. In the knee and hip, loss of joint space with subchondral bone cyst and osteophyte formation is common (Figure 1B).

The cervical and/or lumbar spine may reveal spondylosis, disc space narrowing, and osteophytes. More than 50% of people aged > 65 years have radiologic evidence of OA. However, radiographic evidence of OA is at least twice as common as symptomatic OA, warranting careful consideration when contemplating treatment.⁷

Pathogenesis

Normal articular cartilage is a complex tissue composed of extracellular matrix and chondrocytes. Under ideal conditions, hemostasis is maintained with balance between degradation and synthesis of extracellular matrix proteins. In the aging cartilage, a reduction of total proteoglycan synthesis occurs, decreasing its capacity to retain water. Matrix proteins are modified, leading to the accumulation of advanced glycation end products (AGEs). This process is irreversible, and AGEs cannot be removed from the articular cartilage. Chondrocytes respond to AGEs with increased catabolic activity and cytokine release. Initial chondral edema and matrix degradation leads to stress fractures in the collagen network and fissuring of the cartilage. Eventually, the microfractures lead to fragmenting of the cartilage, formation of loose bodies, and synovial inflammation. Sclerosis occurs in the subchondral bone, with accelerated bone turnover leading to osteophyte formation.⁸

Treatment

Unfortunately, no pharmacologic or nonpharmacologic therapy has been shown to reverse or halt the progression of OA. A comprehensive approach to the treatment of patients with OA is imperative for reducing disability and improving quality of life. Several sources have published guidelines for the management of OA.^9-11 More recently, comprehensive clinical practice guidelines have been published regarding nonsurgical management of hip and knee OA in the veteran population.¹²

Initially, a conservative approach is generally recommended with reduction of modifiable risk factors and patient education. Weight loss, aerobic conditioning, and physical therapy can improve function and stability. Notably, a weight reduction of 5% has been associated with an 18% to 24% improvement in knee OA.⁶ A supervised walking exercise program can be extremely beneficial for patients, with several studies showing improvement in pain, ambulatory function, and psychological well-being. Bracing devices and orthotic footwear can be helpful for compartmental unloading of the knee. The use of ambulatory assist devices (eg, canes, walkers) and splinting may also be of benefit. Topical lidocaine, capsaicin, and topical nonsteroidal anti-inflammatory drugs (NSAIDs) therapy can be useful adjuncts.

Medications are used mainly to provide analgesia and improve function while causing the fewest adverse effects (AEs) (Table 2). Contrary to conventional teaching, acetaminophen may not be as effective in the treatment of OA as previously thought. A recently published metaanalysis comparing treatments for knee OA revealed acetaminophen to be the least effective agent.¹³ Another meta-analysis showed that acetaminophen provided clinically insignificant pain relief in OA of the hip and knee.¹⁴ However, acetaminophen may be useful in the treatment of mild OA or in patients with contraindications to other oral therapies. Nonsteroidal anti-inflammatory drug therapy is more effective in a patient with inflammatory OA symptoms (eg, effusion, erosive OA) and can be added to acetaminophen if ineffective alone. Gastrointestinal protection against ulceration may be warranted, and use of NSAIDs may be contraindicated in the patient with high bleeding risk, renal insufficiency, or cardiovascular disease. In patients with low cardiac risk, celecoxib can be effective. Patients who have a contraindication to NSAIDs may find benefit from other analgesic agents, such as tramadol or duloxetine. Intra-articular corticosteroid injections can be particularly helpful for patients with a single osteoarthritic joint that has been unresponsive to oral or topical analgesics. Opioid analgesics may be used as a last resort when all other agents and therapies have failed. Most patients who require opioid therapy are awaiting surgical repair or are not surgical candidates.

Use of nutritional supplements such as glucosamine and chondroitin sulfate in the treatment of primary knee OA is controversial. These agents are not regulated by the FDA and their potency, purity, and safety are not guaranteed. Furthermore, the bioavailability of oral glucosamine and chondroitin sulfate is particularly poor, and studies have revealed conflicting evidence on their ability to reduce pain in patients with OA. Nonetheless, some evidence exists for cartilage proteoglycan integration and synthesis with glucosamine and chondroitin compounds. Most patients taking these supplements experience few AEs, and some report good responses to therapy. Some patients allergic to shellfish may experience a reaction to glucosamine products.

Hyaluronate injections can be recommended for patients with moderate OA who have failed standard medical treatment. Most clinical trials of hyaluronate suggest an analgesic benefit comparable with NSAID therapy and corticosteroid injections, but high-quality studies are lacking.

Colchicine may be effective in patients with inflammatory or noninflammatory OA. Two small studies showed colchicine to be beneficial in the treatment of primary OA of the knee.^15,16 Hydroxychloroquine may be helpful in the treatment of inflammatory OA.

Loss of joint function or severe pain refractory to medical treatment in a patient with OA likely requires surgical intervention. Patients who have difficulty ambulating more than a reasonable distance (ie, 1 block) or cannot stand in place for more than several minutes due to severe pain should be considered for total joint replacement. Patients often report awaking with severe pain at night or pain that significantly impedes their activities of daily living. In these patients, total joint replacement can be extremely beneficial and life altering.

Conclusion

Osteoarthritis is the most common arthritic disease and has a very high prevalence in the veteran population. Aging, obesity, prior trauma, and activity level are the common risk factors for the development of OA. Patterns of disease are recognizable by history, examination, and prominent radiographic features. Causes of secondary OA are important to recognize and treat. The pathogenesis of OA involves a disrupted homeostatic process leading to cartilage degradation, microfracture, subchondral sclerosis, and osteophyte formation. Treatment is unique to the individual and should include a comprehensive strategy involving patient education, exercise or physical therapy, and analgesia. Patients with severe osteoarthritis that significantly impacts activities of daily living may benefit from surgery.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Osteoarthritis (OA) is one of the most common diseases affecting the general population and is characterized by progressive, noninflammatory degenerative changes primarily involving the hips, knees, spine, hands, and feet. Among veterans the incidence and prevalence of OA is considerably higher than the incidence found in the general population. A study examining active-duty service members between 1999 and 2008 reported a 19-fold higher incidence in service members aged > 40 years compared with those aged < 20 years.1 In addition, women and African American service members seem to have a higher incidence of OA compared with other populations. Overall, the economic burden of OA is estimated to approach or exceed $60 billion annually and will continue to increase due to longer life expectancies in veterans.^2,3 Much of this burden relates to a lack of disease-modifying treatment and inadequacy of analgesic therapy.

Patterns of Osteoarthritis

The strongest risk factor associated with OA is age. Osteoarthritis is the most common cause of pain and disability in the elderly population.⁴ A heritable component seems to be associated with primary OA as shown by family risk studies.⁵ Estrogenic effects seem to protect younger women, whereas postmenopausal women are at greater risk after age 50 years. Previous joint trauma and activities have a large impact on the risk of developing OA later, particularly those activities and occupations requiring high-impact joint loading, such as those often seen in veterans. Other modifiable risk factors include smoking and obesity. The risk for knee OA has been found to increase 30-fold in patients with a body mass index > 30.⁶

Several OA disease patterns exist. The disorder can be characterized as primary or secondary. Primary OA classically presents in the aging male or postmenopausal female involving the apophyseal joints of the lumbar and cervical spine; base of the thumb (first carpometacarpal,[CMC] joint); proximal or distal interphalangeal joints (PIPs and DIPs) of the hand, knee, or hip; or the first metatarsophalangeal joint. The disease may be localized to 1 joint (localized OA) or involve multiple joints (generalized OA). The disease is more common in men aged < 45 years and more common in women aged > 45 years. In either sex, progression with age is a prominent feature.

Rarely, patients may present with inflammatory arthritis in a distribution typical of OA that is not associated with psoriasis or another disease. This form is known as inflammatory or erosive OA. A minority of cases present with rapidly progressive hip or knee degeneration, the cause of which is unknown. Osteoarthritis involving the metacarpophalangeal joints (MCPs), wrists, elbows, shoulders, or ankles is much less common. Patients with radiographic evidence of OA at these sites should be evaluated for a cause of secondary OA.

Patients often develop secondary OA in the setting of inflammatory arthritis, crystal-induced arthritis, and other systemic diseases. Causes of secondary OA should be considered when OA manifests in an atypical joint. Common causes of secondary OA are outlined in Table 1. A careful history may undercover a prior diagnosis of gout, calcium pyrophosphate deposition disease, or infectious arthritis in the affected joint. An important metabolic cause of secondary OA is hemochromatosis, which can lead to osteophytic change primarily in the second and third MCPs. Patients with diabetes mellitus-associated neuropathy may develop destructive changes in the foot (Charcot joint).

Symptoms and Examination

Osteoarthritis encompasses a wide spectrum of common conditions with similar pathophysiology. Most of these conditions share similar historic features, including pain during or after use and stiffness after prolonged periods of inactivity. Other common symptoms include swelling, joint locking or “cracking,” instability, and joint fatigue. Patients may perceive OA discomfort in different ways. Whereas one patient with knee OA may describe a sharp, gnawing pain, another may experience painless swelling and instability. Although OA is mainly considered a localized disease, patients may present with multiple areas of pain, suggesting a more generalized pattern. Patients with OA may have short periods of morning stiffness and “gelling,” but prolonged stiffness suggests the presence of inflammatory arthritis.

Examination of the osteoarthritic joint is performed with thorough palpation and range of motion testing. Evidence of joint swelling may be present near the joint line with pain on palpation. Palpable crepitus is commonly noted with restricted range of motion, usually inducing pain at the maximal range. Osteophytes or chondrophytes at the joint line may be tender and are commonly mistaken for joint swelling. In the hands, bony hypertrophy of the PIP and DIP joints may be noted (Bouchard’s and Heberden’s nodes, respectively). Pain at the base of the thumb is a common complaint in patients with OA of the CMC joint.

Most cases of OA can be diagnosed by taking a history and a physical examination without further investigation; however, plain radiographs are frequently obtained to confirm the diagnosis. Joint inflammation, when present, is usually mild. Occasionally, patients may present with evidence of warmth, effusion, and severe pain with restriction of motion. Patients with these symptoms should undergo prompt arthrocentesis to rule out infection, crystal-associated arthritis, hemarthrosis, or other inflammatory causes.

Radiographic Features

Plain radiographs are extremely helpful in denoting the extent of OA in a particular joint. Radiographic features of OA include narrowing of the joint space, osteophyte formation, and subchondral bone abnormalities. Narrowing of the joint space and alignment abnormalities occur due to loss of articular cartilage. Changes in the subchondral bone include sclerosis and cystic lesions. Erosive changes, ankylosis, and calcification of the articular cartilage are typically absent.

In the hands, a particular pattern is noted involving the PIP and DIP joints with characteristic sparing of the MCPs (Figure 1A). The first CMC joint is also commonly involved, with bony osteophyte formation and joint space loss. In the knee and hip, loss of joint space with subchondral bone cyst and osteophyte formation is common (Figure 1B).

The cervical and/or lumbar spine may reveal spondylosis, disc space narrowing, and osteophytes. More than 50% of people aged > 65 years have radiologic evidence of OA. However, radiographic evidence of OA is at least twice as common as symptomatic OA, warranting careful consideration when contemplating treatment.⁷

Pathogenesis

Normal articular cartilage is a complex tissue composed of extracellular matrix and chondrocytes. Under ideal conditions, hemostasis is maintained with balance between degradation and synthesis of extracellular matrix proteins. In the aging cartilage, a reduction of total proteoglycan synthesis occurs, decreasing its capacity to retain water. Matrix proteins are modified, leading to the accumulation of advanced glycation end products (AGEs). This process is irreversible, and AGEs cannot be removed from the articular cartilage. Chondrocytes respond to AGEs with increased catabolic activity and cytokine release. Initial chondral edema and matrix degradation leads to stress fractures in the collagen network and fissuring of the cartilage. Eventually, the microfractures lead to fragmenting of the cartilage, formation of loose bodies, and synovial inflammation. Sclerosis occurs in the subchondral bone, with accelerated bone turnover leading to osteophyte formation.⁸

Treatment

Unfortunately, no pharmacologic or nonpharmacologic therapy has been shown to reverse or halt the progression of OA. A comprehensive approach to the treatment of patients with OA is imperative for reducing disability and improving quality of life. Several sources have published guidelines for the management of OA.^9-11 More recently, comprehensive clinical practice guidelines have been published regarding nonsurgical management of hip and knee OA in the veteran population.¹²

Initially, a conservative approach is generally recommended with reduction of modifiable risk factors and patient education. Weight loss, aerobic conditioning, and physical therapy can improve function and stability. Notably, a weight reduction of 5% has been associated with an 18% to 24% improvement in knee OA.⁶ A supervised walking exercise program can be extremely beneficial for patients, with several studies showing improvement in pain, ambulatory function, and psychological well-being. Bracing devices and orthotic footwear can be helpful for compartmental unloading of the knee. The use of ambulatory assist devices (eg, canes, walkers) and splinting may also be of benefit. Topical lidocaine, capsaicin, and topical nonsteroidal anti-inflammatory drugs (NSAIDs) therapy can be useful adjuncts.

Medications are used mainly to provide analgesia and improve function while causing the fewest adverse effects (AEs) (Table 2). Contrary to conventional teaching, acetaminophen may not be as effective in the treatment of OA as previously thought. A recently published metaanalysis comparing treatments for knee OA revealed acetaminophen to be the least effective agent.¹³ Another meta-analysis showed that acetaminophen provided clinically insignificant pain relief in OA of the hip and knee.¹⁴ However, acetaminophen may be useful in the treatment of mild OA or in patients with contraindications to other oral therapies. Nonsteroidal anti-inflammatory drug therapy is more effective in a patient with inflammatory OA symptoms (eg, effusion, erosive OA) and can be added to acetaminophen if ineffective alone. Gastrointestinal protection against ulceration may be warranted, and use of NSAIDs may be contraindicated in the patient with high bleeding risk, renal insufficiency, or cardiovascular disease. In patients with low cardiac risk, celecoxib can be effective. Patients who have a contraindication to NSAIDs may find benefit from other analgesic agents, such as tramadol or duloxetine. Intra-articular corticosteroid injections can be particularly helpful for patients with a single osteoarthritic joint that has been unresponsive to oral or topical analgesics. Opioid analgesics may be used as a last resort when all other agents and therapies have failed. Most patients who require opioid therapy are awaiting surgical repair or are not surgical candidates.

Use of nutritional supplements such as glucosamine and chondroitin sulfate in the treatment of primary knee OA is controversial. These agents are not regulated by the FDA and their potency, purity, and safety are not guaranteed. Furthermore, the bioavailability of oral glucosamine and chondroitin sulfate is particularly poor, and studies have revealed conflicting evidence on their ability to reduce pain in patients with OA. Nonetheless, some evidence exists for cartilage proteoglycan integration and synthesis with glucosamine and chondroitin compounds. Most patients taking these supplements experience few AEs, and some report good responses to therapy. Some patients allergic to shellfish may experience a reaction to glucosamine products.

Hyaluronate injections can be recommended for patients with moderate OA who have failed standard medical treatment. Most clinical trials of hyaluronate suggest an analgesic benefit comparable with NSAID therapy and corticosteroid injections, but high-quality studies are lacking.

Colchicine may be effective in patients with inflammatory or noninflammatory OA. Two small studies showed colchicine to be beneficial in the treatment of primary OA of the knee.^15,16 Hydroxychloroquine may be helpful in the treatment of inflammatory OA.

Loss of joint function or severe pain refractory to medical treatment in a patient with OA likely requires surgical intervention. Patients who have difficulty ambulating more than a reasonable distance (ie, 1 block) or cannot stand in place for more than several minutes due to severe pain should be considered for total joint replacement. Patients often report awaking with severe pain at night or pain that significantly impedes their activities of daily living. In these patients, total joint replacement can be extremely beneficial and life altering.

Conclusion

Osteoarthritis is the most common arthritic disease and has a very high prevalence in the veteran population. Aging, obesity, prior trauma, and activity level are the common risk factors for the development of OA. Patterns of disease are recognizable by history, examination, and prominent radiographic features. Causes of secondary OA are important to recognize and treat. The pathogenesis of OA involves a disrupted homeostatic process leading to cartilage degradation, microfracture, subchondral sclerosis, and osteophyte formation. Treatment is unique to the individual and should include a comprehensive strategy involving patient education, exercise or physical therapy, and analgesia. Patients with severe osteoarthritis that significantly impacts activities of daily living may benefit from surgery.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Psoriasis is a commonly encountered systemic condition, usually presenting with chronic erythematous plaques with an overlying silvery white scale.¹ Extracutaneous manifestations, such as joint or spine (axial) involvement, can occur along with this skin disorder. Psoriatic arthritis (PsA) is a chronic, heterogeneous disorder characterized by inflammatory arthritis in patients with psoriasis.^2,3 Until recently treatment of PsA has been limited to a few medications.

Continuing investigations into the pathogenesis of PsA have revealed new treatment options, targeting molecules at the cellular level. Over the past few years, additional medications have been approved, giving providers more options in treating patients with psoriasis and PsA. Furthermore, a multidisciplinary approach by both rheumatologists and dermatologists in evaluating and managing patients at VA clinics has helped optimize care of these patients by providing timely evaluation and treatment at the same visit.

Psoriasis Presentation and Diagnosis

Genetic predisposition and certain environmental factors (trauma, infection, medications) are known to trigger psoriasis, which can present in many forms.⁴ Chronic plaque psoriasis, or psoriasis vulgaris, is the most common skin pattern with a classic presentation of sharply demarcated erythematous plaques with overlying silver scale.⁴ It affects the scalp, lower back, umbilicus, genitals, and extensor surfaces of the elbows and knees. Guttate psoriasis is recognized by its multiple small papules and plaques in a droplike pattern. Pustular psoriasis usually presents with widespread pustules. On the other hand, erythrodermic psoriasis manifests as diffuse erythema involving multiple skin areas.⁴ Erythematous psoriatic plaques, which are predominantly in the intertriginous areas or skin folds (inguinal, perineal, genital, intergluteal, axillary, or inframammary), are known as inverse psoriasis.

A psoriasis diagnosis is made by taking a history and a physical examination. Rarely, a skin biopsy of the lesions will be required for an atypical presentation. The course of the disease is unpredictable, variable, and dependent on the type of psoriasis. Psoriasis vulgaris is a chronic condition, whereas guttate psoriasis is often self-limited.⁴ A poorer prognosis is seen in patients with erythrodermic and generalized pustular psoriasis.⁴

Psoriatic Arthritis Presentation, Classification, and Diagnosis

Prevalence of PsA is not known, but it is estimated to be from 0.3% to 1% of the U.S. population. In the psoriasis population, PsA is reported to range from 7% to 42%,³ although more recently, these numbers have been found to be in the 15% to 25% range (unpublished observations). This type of inflammatory arthritis can develop at any age but usually is seen between the ages of 30 and 50 years, with men being affected equally or a little more than are women.³ Clinical symptoms usually include pain and stiffness of affected joints, > 30 minutes of morning stiffness, and fatigue.

The presentation of joint involvement can vary widely. Five subtypes of arthritis were identified by Moll and Wright in 1973, which included arthritis with predominant distal interphalangeal involvement, arthritis mutilans, symmetric polyarthritis (> 5 joints), asymmetric oligoarthritis (1-4 joints), and predominant spondylitis (axial).⁵ Patients with PsA may also have evidence of spondylitis (inflammation of vertebra) or sacroiliitis (inflammation of the sacroiliac joints) with back pain > 3 months, hip or buttock pain, nighttime pain, or pain that improves with activity but worsens with rest.6 The cervical spine is more frequently involved than is the lumbar spine in patients with PsA.³

Psoriatic arthritis can have a diverse presentation not only with the affected joints, but also involving nails, tendons, and ligaments. An entire digit of the hand or foot can become swollen, known as dactylitis, or “sausage digit.” Inflammation at the insertion of tendons or ligaments, known as enthesitis, is also seen in PsA. Most common sites include the Achilles tendon, plantar fascia, and ligamentous insertions around the pelvic bones.³ Nail changes that are typically seen in patients with psoriasis can be seen in PsA as well, including pitting, ridging, hyperkeratosis, and onycholysis.³ Ocular inflammation which is classically seen with other spondyloarthropathies, can be seen in patients with PsA as well, frequently manifesting as conjunctivitis.^2,3

Psoriatic arthritis is commonly classified under the broader category of seronegative spondyloarthropathies, given the low frequency of a positive rheumatoid factor.³ Currently, there are no laboratory tests that can help with a PsA diagnosis.³ Acute-phase reactants such as erythrocyte sedimentation rate and C-reactive protein may be elevated, indicating active inflammation.

Radiographic data, such as X-rays of the hands and feet, can confirm the clinical distribution of joint involvement and show evidence of erosive changes. Further destructive changes include osteolysis (bone resorption) that may cause the classic pencil-in-cup deformity, typically seen in arthritis mutilans (Figure 1).³ Other radiographic evidence of PsA can include proliferative changes with new bone formation seen along the shaft of the metacarpal and metatarsal bones.³ Patients with axial involvement can have evidence of asymmetric sacroiliitis, which can be seen on radiographs. Asymmetric syndesmophytes, or bony outgrowths, can also be seen throughout the axial spine.³

Diagnosis is based on the history and clinical presentation of a patient with the help of laboratory work and radiographs. Other forms of arthritis (such as rheumatoid arthritis, crystal arthropathies, osteoarthritis, ankylosing spondylitis) should be excluded. Given the varied presentation of PsA, classification criteria have been developed to assist in clinical research. Classification Criteria for Psoriatic Arthritis (CASPAR) have been developed and validated as an adjunct to clinical diagnosis and a source for clinical research (Table 1).⁷ Musculoskeletal pain in patients with psoriasis can be due to causes other than PsA, such as osteoarthritis and gout. A close working relationship in a combined rheumatology/dermatology clinic is vital to providing optimal diagnostic and treatment care for patients with psoriasis and PsA.⁸

The etiology of PsA is currently unknown, although many genetic, environmental, and immunologic factors have been identified that play a role in the pathogenesis of the disease. In this setting, immunologically mediated processes that cause inflammation occur in the synovium of joints, enthesium, bone, and skin of patients with PsA.⁹ Studies have shown that activated T cells and T-cell–derived cytokines play an important role in cartilage degradation, joint damage, and stimulating bone resorption.⁹

One particular proinflammatory cytokine, tumor necrosis factor alpha (TNFα), has been the target for many treatment modalities for several years. With new and ongoing research into the PsA pathogenesis, other treatment options have been discovered, targeting different cytokines and T cells that are involved in the disease process. This has led to drug trials and recent FDA approvals of several new medications, which provide further options for clinicians in managing and treating PsA.

Management of Psoriasis

Choice of therapy is determined by the extent and severity of psoriasis (body surface area [BSA] involvement) as well as the patient’s comorbidities and preferences.⁴ Providers have a wide spectrum of effective therapies to prescribe, both topically and systemically. Topical therapy options include corticosteroids, vitamin D3 and analogs (calcipotriene), anthralin, tar, tazarotene (third-generation retinoid), and calcineurin inhibitors (tacromlimus).⁴ Phototherapy with or without saltwater baths helps improve skin lesions.

These treatments are beneficial for all patients with psoriasis, but the disease can be controlled with monotherapy in patients with mild-to-moderate disease (< 10% BSA). Limiting these treatment options are some long-term effects of the medications because of the potential for toxicity as well as decreasing efficacy of the medication over time.4 For patients with more BSA involvement (> 10%), systemic treatment options include methotrexate (MTX), systemic retinoids (acitretin), calcineurin inhibitors (cyclosporine), and biologics. Many of these systemic treatment options overlap for patients with both psoriasis and PsA, and topical treatments can be used adjunctively to better control the skin disease.

Management of Psoriatic Arthritis

It is important to identify PsA and begin treatment early, because it has been shown that patients tend to fare better in their disease course if treated early.¹⁰ Once a diagnosis of PsA is made, disease activity needs to be determined by clinical examination and radiographs of joints. Scoring systems, by assessing bone erosions and deformities on joint radiographs, can aide with this assessment. Based on these, PsA can be categorized as mild, moderate, or severe. Several disease activity measures that have been developed for clinical trials in monitoring of disease activity can be used as an aide in the office setting. These tools are still being studied to determine the optimal measure of disease activity.

NSAIDs and Glucocorticoids

Controlling inflammation and providing pain relief are the primary treatment goals for patients with PsA. In mild, predominantly peripheral PsA, nonsteroidal antiinflammatory drugs (NSAIDs) can be used, but they do not halt disease progression. If the disease is controlled and not progressing, NSAIDs may be used as the only treatment. However, if symptoms persist and/or there is more joint involvement, the next level of therapy should be sought. Intra-articular corticosteroids for symptomatic relief can be given if only a few joints are affected. Oral corticosteroids can be used occasionally in patients with multiple joint aches, but they are typically avoided or tapered slowly to avoid worsening the patient’s skin psoriasis or having it evolve into a more severe form, such as pustular psoriasis.¹⁰ All these treatments can alleviate symptoms, but they do not prevent the progression of disease.

Disease-Modifying Antirheumatic Drugs

For patients who fail NSAIDs or present initially with more joint involvement (polyarthritis or > 5 swollen joints), traditional disease-modifying antirheumatic drugs (DMARDs) should be started (Table 2). Methotrexate is one of the first-line DMARD prescriptions. It is commonly used because of its effectiveness in treating both skin and joint involvement, despite limited evidence of its efficacy in controlled clinical trials for slowing the progression of joint damage in PsA.^2,9-11 Methotrexate can be given orally or subcutaneously (SC) every week. Routine laboratory monitoring is required given the known effects of MTX on liver and bone marrow suppression. Clinical monitoring is needed as well due to its well-known risk for pulmonary toxicity and teratogenicity.²

Leflunomide is another traditional oral DMARD that is administered daily. It has be shown to be effective in PsA, with only a modest effect in improving skin lesions.¹² Laboratory monitoring is identical to that required with MTX. Adverse effects (AEs) include diarrhea and increased risk of elevated transaminases.⁹ Sulfasalazine (SSZ) is also used as a traditional DMARD and shown to have an effective clinical response in treating peripheral arthritis but not in axial or skin disease.^9,12 Not all studies have shown effective responses to SSZ. The primary AE is gastrointestinal, making this a frequently discontinued medication.² Cyclosporine is more commonly used in psoriasis but can be used on its own or with MTX for treating patients with PsA.¹⁰ It is often not tolerated well and frequently discontinued, due to major AEs, including hypertension and renal dysfunction.^2,10

These traditional DMARDs are usually given for 3 to 6 months.¹³ After this initial period, the patient’s clinical response is reassessed, and the need for changing therapy to another DMARD or biologic is determined.

Biologic Therapies

With the discovery of TNFα as a potent cytokine in inflammatory arthritis came a new class of medications that has provided patients and providers with more effective treatment options. This category of medications is known as tumor necrosis factor inhibitors (TNFis). Five medications have been developed that target TNFα, each in its own way: etanercept, infliximab, adalimumab, golimumab, and certrolizumab pegol. These medications were initially studied in patients with rheumatoid arthritis, with further clinical trials performed for treatment of PsA. Each is prescribed differently: Adalimumab and certrolizumab are given SC every 2 weeks, etanercept is given weekly, and golimumab is given once a month. Infliximab is the only medication prescribed as an infusion, which is administered every 8 weeks after receiving 3 loading doses.

Studies have shown that all TNFis are effective in treating PsA: improving joint disease activity, inhibiting progression of structural damage, and improving function and overall quality of life^.10 The TNFi drugs also improve psoriasis along with dactylitis, enthesitis, and nail changes.¹³ Patients with
axial disease benefit from TNFi, but the evidence of TNFi effectiveness is extrapolated from studies in axial spondyloarthritis.^13,14 Tumor necrosis
factor inhibitors can be used as monotherapy, although there is some evidence for using TNFi drugs with MTX in PsA. Combination therapy can potentially prolong the survival of the TNFi drug or prevent formation of antidrug antibodies.^14,15

The current evidence for monotherapy vs combination therapy in patients with PsA is not consistent, and no formal guidelines have been developed to guide physicians one way or another. The TNFi drugs are generally well tolerated, although the patient needs to learn how to self-inject if given the SC route. Adverse effects include infusion or injection site reactions and infections. Prior to starting a TNFi, it is prudent to screen for latent tuberculosis infection as well as hepatitis B and C, given the risk of reactivation. Clinical response is monitored for 3 months, and if remission or low disease activity is not reached, a different TNFi may be tried.¹³ Importantly, patients receiving infliximab without clinical improvement in 3 months may have their dose and frequency increased before switching to an alternative TNFi. Some studies show that a trial of a second TNFi has a less potent response than with a first TNFi, and the drug survival is shorter in duration.¹³

One of the newest biologic agents approved for treating PsA is ustekinumab, a human monoclonal antibody (MAB) that inhibits receptor binding of cytokines interleukin (IL)-12 and IL-23. These cytokines have been identified in patients with psoriasis and PsA as further promoting inflammation. Ustekinumab recently received approval for the treatment of PsA and is given SC every 12 weeks after 2 initial doses. Further studies have also confirmed ustekinumab significantly suppressed radiographic progression of joint damage in patients with active PsA.¹⁵ Notable AEs included infections, but there have been no cases of tuberculosis or opportunistic infections reported.¹⁶

The most recent FDA-approved medication for PsA is apremilast. It is a phosphodiesterase-4 inhibitor, which causes the suppression of other proinflammatory mediators and cytokines active in the immune system.¹⁰ It is given orally, uptitrating the doses over a few days until the twice-daily maintenance dosing is achieved. It is generally well tolerated with nausea and diarrhea as the most common AEs.¹⁷ Further studies need to be conducted to assess whether this agent is able to prevent or decrease joint damage.

Other potential treatment options are currently undergoing trials to assess their efficacy and safety in treating psoriasis and/or PsA. One class targets the IL-17 cytokine pathway and includes brodalumab, a monoclonal antibody (MAB) anti-IL-17 receptor, ixekizumab and secukinumab, both MABs anti-IL-17A. Secukinumab has already received FDA approval for the treatment of plaque psoriasis (2015). Other agents currently undergoing trials are abatacept (cytotoxic T-lymphocyte antigen 4-Ig), a recombinant human fusion protein that blocks the co-stimulation of T cells9 and tofacitinib, a janus kinase inhibitor.¹⁸ Early studies show patients achieving a response with these medications, but further long-term studies are needed.¹⁹

Treatment Recommendations

Treatment approaches differ for patients with only psoriasis and patients with psoriasis and PsA, although some treatment modalities overlap. Recommendations for PsA have been set for each domain affected (Figure 2). The treatment approach is based on several factors, including severity or the degree of disease activity, any joint damage, and the patient’s comorbidities. Certain comorbidities are associated with PsA—cardiovascular disease, obesity, metabolic syndrome, diabetes, inflammatory bowel disease, fatty liver disease, chronic viral infections (hepatitis B or C), and kidney disease. These comorbidities can affect the choice of therapy for the patient.^20,21 Other factors affecting treatment choices include patient preference regarding mode and frequency of administration of the medication, potential AEs, requirements of laboratory monitoring or regular doctor visits, and the cost of medications.^10,22

In treating patients with psoriasis and PsA, a multidisciplinary approach is needed. Because skin manifestations of psoriasis usually develop prior to arthritis symptoms in most patients, primary care providers and dermatologists can routinely screen patients for arthritis.¹⁰ Rheumatologists can confirm arthritis and musculoskeletal involvement, but the treatment and management of these patients will need to be in collaboration with a dermatologist. The goal of comanagement is to choose appropriate therapies that may be able to treat both the skin and musculoskeletal manifestations.

A multidisciplinary approach can also limit polypharmacy, control costs, and reduce AEs. The existence of VA combined rheumatology and dermatology clinics makes this an invaluable experience for the veteran with direct and focused patient management. In addition to controlling disease activity, the goal of treatment is to improve function and the patient’s quality of life, halting structural joint damage to prevent disability.¹⁰ Physical and occupational therapies play an important role in PsA management as does exercise. Patients should be educated about their disease and treatment options discussed. It is also important to identify and reduce significant comorbidities, such as cardiovascular disease, to decrease mortality and improve life expectancy.¹⁰

Conclusion

Psoriasis is a distinct disease entity but can occur along with extracutaneous features. Patients with psoriasis need to be screened for PsA, and it is important to diagnose PsA early to begin appropriate treatment. Disease activity, severity, and any joint damage will determine therapy. Over the past decade, new treatment options have become available that provide more choices for patients than those of the standard DMARDs. The TNFis have proven to be efficacious in treating psoriasis and PsA. With a better understanding of pathogenesis of these diseases, new medications have been discovered targeting different parts of the immune system involved in dysregulation and ultimately inflammation. Additional clinical research is needed to provide physicians with more effective ways of controlling these diseases. Ultimately, the management of PsA is not solely based on medications, but the authors’ VA experience highlights the importance of a multispecialty approach to the management of psoriasis and PsA.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects— before administering pharmacologic therapy to patients.

Psoriasis is a commonly encountered systemic condition, usually presenting with chronic erythematous plaques with an overlying silvery white scale.¹ Extracutaneous manifestations, such as joint or spine (axial) involvement, can occur along with this skin disorder. Psoriatic arthritis (PsA) is a chronic, heterogeneous disorder characterized by inflammatory arthritis in patients with psoriasis.^2,3 Until recently treatment of PsA has been limited to a few medications.

Continuing investigations into the pathogenesis of PsA have revealed new treatment options, targeting molecules at the cellular level. Over the past few years, additional medications have been approved, giving providers more options in treating patients with psoriasis and PsA. Furthermore, a multidisciplinary approach by both rheumatologists and dermatologists in evaluating and managing patients at VA clinics has helped optimize care of these patients by providing timely evaluation and treatment at the same visit.

Psoriasis Presentation and Diagnosis

Genetic predisposition and certain environmental factors (trauma, infection, medications) are known to trigger psoriasis, which can present in many forms.⁴ Chronic plaque psoriasis, or psoriasis vulgaris, is the most common skin pattern with a classic presentation of sharply demarcated erythematous plaques with overlying silver scale.⁴ It affects the scalp, lower back, umbilicus, genitals, and extensor surfaces of the elbows and knees. Guttate psoriasis is recognized by its multiple small papules and plaques in a droplike pattern. Pustular psoriasis usually presents with widespread pustules. On the other hand, erythrodermic psoriasis manifests as diffuse erythema involving multiple skin areas.⁴ Erythematous psoriatic plaques, which are predominantly in the intertriginous areas or skin folds (inguinal, perineal, genital, intergluteal, axillary, or inframammary), are known as inverse psoriasis.

A psoriasis diagnosis is made by taking a history and a physical examination. Rarely, a skin biopsy of the lesions will be required for an atypical presentation. The course of the disease is unpredictable, variable, and dependent on the type of psoriasis. Psoriasis vulgaris is a chronic condition, whereas guttate psoriasis is often self-limited.⁴ A poorer prognosis is seen in patients with erythrodermic and generalized pustular psoriasis.⁴

Psoriatic Arthritis Presentation, Classification, and Diagnosis

Prevalence of PsA is not known, but it is estimated to be from 0.3% to 1% of the U.S. population. In the psoriasis population, PsA is reported to range from 7% to 42%,³ although more recently, these numbers have been found to be in the 15% to 25% range (unpublished observations). This type of inflammatory arthritis can develop at any age but usually is seen between the ages of 30 and 50 years, with men being affected equally or a little more than are women.³ Clinical symptoms usually include pain and stiffness of affected joints, > 30 minutes of morning stiffness, and fatigue.

The presentation of joint involvement can vary widely. Five subtypes of arthritis were identified by Moll and Wright in 1973, which included arthritis with predominant distal interphalangeal involvement, arthritis mutilans, symmetric polyarthritis (> 5 joints), asymmetric oligoarthritis (1-4 joints), and predominant spondylitis (axial).⁵ Patients with PsA may also have evidence of spondylitis (inflammation of vertebra) or sacroiliitis (inflammation of the sacroiliac joints) with back pain > 3 months, hip or buttock pain, nighttime pain, or pain that improves with activity but worsens with rest.6 The cervical spine is more frequently involved than is the lumbar spine in patients with PsA.³

Psoriatic arthritis can have a diverse presentation not only with the affected joints, but also involving nails, tendons, and ligaments. An entire digit of the hand or foot can become swollen, known as dactylitis, or “sausage digit.” Inflammation at the insertion of tendons or ligaments, known as enthesitis, is also seen in PsA. Most common sites include the Achilles tendon, plantar fascia, and ligamentous insertions around the pelvic bones.³ Nail changes that are typically seen in patients with psoriasis can be seen in PsA as well, including pitting, ridging, hyperkeratosis, and onycholysis.³ Ocular inflammation which is classically seen with other spondyloarthropathies, can be seen in patients with PsA as well, frequently manifesting as conjunctivitis.^2,3

Psoriatic arthritis is commonly classified under the broader category of seronegative spondyloarthropathies, given the low frequency of a positive rheumatoid factor.³ Currently, there are no laboratory tests that can help with a PsA diagnosis.³ Acute-phase reactants such as erythrocyte sedimentation rate and C-reactive protein may be elevated, indicating active inflammation.

Radiographic data, such as X-rays of the hands and feet, can confirm the clinical distribution of joint involvement and show evidence of erosive changes. Further destructive changes include osteolysis (bone resorption) that may cause the classic pencil-in-cup deformity, typically seen in arthritis mutilans (Figure 1).³ Other radiographic evidence of PsA can include proliferative changes with new bone formation seen along the shaft of the metacarpal and metatarsal bones.³ Patients with axial involvement can have evidence of asymmetric sacroiliitis, which can be seen on radiographs. Asymmetric syndesmophytes, or bony outgrowths, can also be seen throughout the axial spine.³

Diagnosis is based on the history and clinical presentation of a patient with the help of laboratory work and radiographs. Other forms of arthritis (such as rheumatoid arthritis, crystal arthropathies, osteoarthritis, ankylosing spondylitis) should be excluded. Given the varied presentation of PsA, classification criteria have been developed to assist in clinical research. Classification Criteria for Psoriatic Arthritis (CASPAR) have been developed and validated as an adjunct to clinical diagnosis and a source for clinical research (Table 1).⁷ Musculoskeletal pain in patients with psoriasis can be due to causes other than PsA, such as osteoarthritis and gout. A close working relationship in a combined rheumatology/dermatology clinic is vital to providing optimal diagnostic and treatment care for patients with psoriasis and PsA.⁸

The etiology of PsA is currently unknown, although many genetic, environmental, and immunologic factors have been identified that play a role in the pathogenesis of the disease. In this setting, immunologically mediated processes that cause inflammation occur in the synovium of joints, enthesium, bone, and skin of patients with PsA.⁹ Studies have shown that activated T cells and T-cell–derived cytokines play an important role in cartilage degradation, joint damage, and stimulating bone resorption.⁹

One particular proinflammatory cytokine, tumor necrosis factor alpha (TNFα), has been the target for many treatment modalities for several years. With new and ongoing research into the PsA pathogenesis, other treatment options have been discovered, targeting different cytokines and T cells that are involved in the disease process. This has led to drug trials and recent FDA approvals of several new medications, which provide further options for clinicians in managing and treating PsA.

Management of Psoriasis

Choice of therapy is determined by the extent and severity of psoriasis (body surface area [BSA] involvement) as well as the patient’s comorbidities and preferences.⁴ Providers have a wide spectrum of effective therapies to prescribe, both topically and systemically. Topical therapy options include corticosteroids, vitamin D3 and analogs (calcipotriene), anthralin, tar, tazarotene (third-generation retinoid), and calcineurin inhibitors (tacromlimus).⁴ Phototherapy with or without saltwater baths helps improve skin lesions.

These treatments are beneficial for all patients with psoriasis, but the disease can be controlled with monotherapy in patients with mild-to-moderate disease (< 10% BSA). Limiting these treatment options are some long-term effects of the medications because of the potential for toxicity as well as decreasing efficacy of the medication over time.4 For patients with more BSA involvement (> 10%), systemic treatment options include methotrexate (MTX), systemic retinoids (acitretin), calcineurin inhibitors (cyclosporine), and biologics. Many of these systemic treatment options overlap for patients with both psoriasis and PsA, and topical treatments can be used adjunctively to better control the skin disease.

Management of Psoriatic Arthritis

It is important to identify PsA and begin treatment early, because it has been shown that patients tend to fare better in their disease course if treated early.¹⁰ Once a diagnosis of PsA is made, disease activity needs to be determined by clinical examination and radiographs of joints. Scoring systems, by assessing bone erosions and deformities on joint radiographs, can aide with this assessment. Based on these, PsA can be categorized as mild, moderate, or severe. Several disease activity measures that have been developed for clinical trials in monitoring of disease activity can be used as an aide in the office setting. These tools are still being studied to determine the optimal measure of disease activity.

NSAIDs and Glucocorticoids

Controlling inflammation and providing pain relief are the primary treatment goals for patients with PsA. In mild, predominantly peripheral PsA, nonsteroidal antiinflammatory drugs (NSAIDs) can be used, but they do not halt disease progression. If the disease is controlled and not progressing, NSAIDs may be used as the only treatment. However, if symptoms persist and/or there is more joint involvement, the next level of therapy should be sought. Intra-articular corticosteroids for symptomatic relief can be given if only a few joints are affected. Oral corticosteroids can be used occasionally in patients with multiple joint aches, but they are typically avoided or tapered slowly to avoid worsening the patient’s skin psoriasis or having it evolve into a more severe form, such as pustular psoriasis.¹⁰ All these treatments can alleviate symptoms, but they do not prevent the progression of disease.

Disease-Modifying Antirheumatic Drugs

For patients who fail NSAIDs or present initially with more joint involvement (polyarthritis or > 5 swollen joints), traditional disease-modifying antirheumatic drugs (DMARDs) should be started (Table 2). Methotrexate is one of the first-line DMARD prescriptions. It is commonly used because of its effectiveness in treating both skin and joint involvement, despite limited evidence of its efficacy in controlled clinical trials for slowing the progression of joint damage in PsA.^2,9-11 Methotrexate can be given orally or subcutaneously (SC) every week. Routine laboratory monitoring is required given the known effects of MTX on liver and bone marrow suppression. Clinical monitoring is needed as well due to its well-known risk for pulmonary toxicity and teratogenicity.²

Leflunomide is another traditional oral DMARD that is administered daily. It has be shown to be effective in PsA, with only a modest effect in improving skin lesions.¹² Laboratory monitoring is identical to that required with MTX. Adverse effects (AEs) include diarrhea and increased risk of elevated transaminases.⁹ Sulfasalazine (SSZ) is also used as a traditional DMARD and shown to have an effective clinical response in treating peripheral arthritis but not in axial or skin disease.^9,12 Not all studies have shown effective responses to SSZ. The primary AE is gastrointestinal, making this a frequently discontinued medication.² Cyclosporine is more commonly used in psoriasis but can be used on its own or with MTX for treating patients with PsA.¹⁰ It is often not tolerated well and frequently discontinued, due to major AEs, including hypertension and renal dysfunction.^2,10

These traditional DMARDs are usually given for 3 to 6 months.¹³ After this initial period, the patient’s clinical response is reassessed, and the need for changing therapy to another DMARD or biologic is determined.

Biologic Therapies

With the discovery of TNFα as a potent cytokine in inflammatory arthritis came a new class of medications that has provided patients and providers with more effective treatment options. This category of medications is known as tumor necrosis factor inhibitors (TNFis). Five medications have been developed that target TNFα, each in its own way: etanercept, infliximab, adalimumab, golimumab, and certrolizumab pegol. These medications were initially studied in patients with rheumatoid arthritis, with further clinical trials performed for treatment of PsA. Each is prescribed differently: Adalimumab and certrolizumab are given SC every 2 weeks, etanercept is given weekly, and golimumab is given once a month. Infliximab is the only medication prescribed as an infusion, which is administered every 8 weeks after receiving 3 loading doses.

Studies have shown that all TNFis are effective in treating PsA: improving joint disease activity, inhibiting progression of structural damage, and improving function and overall quality of life^.10 The TNFi drugs also improve psoriasis along with dactylitis, enthesitis, and nail changes.¹³ Patients with
axial disease benefit from TNFi, but the evidence of TNFi effectiveness is extrapolated from studies in axial spondyloarthritis.^13,14 Tumor necrosis
factor inhibitors can be used as monotherapy, although there is some evidence for using TNFi drugs with MTX in PsA. Combination therapy can potentially prolong the survival of the TNFi drug or prevent formation of antidrug antibodies.^14,15

The current evidence for monotherapy vs combination therapy in patients with PsA is not consistent, and no formal guidelines have been developed to guide physicians one way or another. The TNFi drugs are generally well tolerated, although the patient needs to learn how to self-inject if given the SC route. Adverse effects include infusion or injection site reactions and infections. Prior to starting a TNFi, it is prudent to screen for latent tuberculosis infection as well as hepatitis B and C, given the risk of reactivation. Clinical response is monitored for 3 months, and if remission or low disease activity is not reached, a different TNFi may be tried.¹³ Importantly, patients receiving infliximab without clinical improvement in 3 months may have their dose and frequency increased before switching to an alternative TNFi. Some studies show that a trial of a second TNFi has a less potent response than with a first TNFi, and the drug survival is shorter in duration.¹³

One of the newest biologic agents approved for treating PsA is ustekinumab, a human monoclonal antibody (MAB) that inhibits receptor binding of cytokines interleukin (IL)-12 and IL-23. These cytokines have been identified in patients with psoriasis and PsA as further promoting inflammation. Ustekinumab recently received approval for the treatment of PsA and is given SC every 12 weeks after 2 initial doses. Further studies have also confirmed ustekinumab significantly suppressed radiographic progression of joint damage in patients with active PsA.¹⁵ Notable AEs included infections, but there have been no cases of tuberculosis or opportunistic infections reported.¹⁶

The most recent FDA-approved medication for PsA is apremilast. It is a phosphodiesterase-4 inhibitor, which causes the suppression of other proinflammatory mediators and cytokines active in the immune system.¹⁰ It is given orally, uptitrating the doses over a few days until the twice-daily maintenance dosing is achieved. It is generally well tolerated with nausea and diarrhea as the most common AEs.¹⁷ Further studies need to be conducted to assess whether this agent is able to prevent or decrease joint damage.

Other potential treatment options are currently undergoing trials to assess their efficacy and safety in treating psoriasis and/or PsA. One class targets the IL-17 cytokine pathway and includes brodalumab, a monoclonal antibody (MAB) anti-IL-17 receptor, ixekizumab and secukinumab, both MABs anti-IL-17A. Secukinumab has already received FDA approval for the treatment of plaque psoriasis (2015). Other agents currently undergoing trials are abatacept (cytotoxic T-lymphocyte antigen 4-Ig), a recombinant human fusion protein that blocks the co-stimulation of T cells9 and tofacitinib, a janus kinase inhibitor.¹⁸ Early studies show patients achieving a response with these medications, but further long-term studies are needed.¹⁹

Treatment Recommendations

Treatment approaches differ for patients with only psoriasis and patients with psoriasis and PsA, although some treatment modalities overlap. Recommendations for PsA have been set for each domain affected (Figure 2). The treatment approach is based on several factors, including severity or the degree of disease activity, any joint damage, and the patient’s comorbidities. Certain comorbidities are associated with PsA—cardiovascular disease, obesity, metabolic syndrome, diabetes, inflammatory bowel disease, fatty liver disease, chronic viral infections (hepatitis B or C), and kidney disease. These comorbidities can affect the choice of therapy for the patient.^20,21 Other factors affecting treatment choices include patient preference regarding mode and frequency of administration of the medication, potential AEs, requirements of laboratory monitoring or regular doctor visits, and the cost of medications.^10,22

In treating patients with psoriasis and PsA, a multidisciplinary approach is needed. Because skin manifestations of psoriasis usually develop prior to arthritis symptoms in most patients, primary care providers and dermatologists can routinely screen patients for arthritis.¹⁰ Rheumatologists can confirm arthritis and musculoskeletal involvement, but the treatment and management of these patients will need to be in collaboration with a dermatologist. The goal of comanagement is to choose appropriate therapies that may be able to treat both the skin and musculoskeletal manifestations.

A multidisciplinary approach can also limit polypharmacy, control costs, and reduce AEs. The existence of VA combined rheumatology and dermatology clinics makes this an invaluable experience for the veteran with direct and focused patient management. In addition to controlling disease activity, the goal of treatment is to improve function and the patient’s quality of life, halting structural joint damage to prevent disability.¹⁰ Physical and occupational therapies play an important role in PsA management as does exercise. Patients should be educated about their disease and treatment options discussed. It is also important to identify and reduce significant comorbidities, such as cardiovascular disease, to decrease mortality and improve life expectancy.¹⁰

Conclusion

Psoriasis is a distinct disease entity but can occur along with extracutaneous features. Patients with psoriasis need to be screened for PsA, and it is important to diagnose PsA early to begin appropriate treatment. Disease activity, severity, and any joint damage will determine therapy. Over the past decade, new treatment options have become available that provide more choices for patients than those of the standard DMARDs. The TNFis have proven to be efficacious in treating psoriasis and PsA. With a better understanding of pathogenesis of these diseases, new medications have been discovered targeting different parts of the immune system involved in dysregulation and ultimately inflammation. Additional clinical research is needed to provide physicians with more effective ways of controlling these diseases. Ultimately, the management of PsA is not solely based on medications, but the authors’ VA experience highlights the importance of a multispecialty approach to the management of psoriasis and PsA.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects— before administering pharmacologic therapy to patients.

Psoriasis is a commonly encountered systemic condition, usually presenting with chronic erythematous plaques with an overlying silvery white scale.¹ Extracutaneous manifestations, such as joint or spine (axial) involvement, can occur along with this skin disorder. Psoriatic arthritis (PsA) is a chronic, heterogeneous disorder characterized by inflammatory arthritis in patients with psoriasis.^2,3 Until recently treatment of PsA has been limited to a few medications.

Continuing investigations into the pathogenesis of PsA have revealed new treatment options, targeting molecules at the cellular level. Over the past few years, additional medications have been approved, giving providers more options in treating patients with psoriasis and PsA. Furthermore, a multidisciplinary approach by both rheumatologists and dermatologists in evaluating and managing patients at VA clinics has helped optimize care of these patients by providing timely evaluation and treatment at the same visit.

Psoriasis Presentation and Diagnosis

Genetic predisposition and certain environmental factors (trauma, infection, medications) are known to trigger psoriasis, which can present in many forms.⁴ Chronic plaque psoriasis, or psoriasis vulgaris, is the most common skin pattern with a classic presentation of sharply demarcated erythematous plaques with overlying silver scale.⁴ It affects the scalp, lower back, umbilicus, genitals, and extensor surfaces of the elbows and knees. Guttate psoriasis is recognized by its multiple small papules and plaques in a droplike pattern. Pustular psoriasis usually presents with widespread pustules. On the other hand, erythrodermic psoriasis manifests as diffuse erythema involving multiple skin areas.⁴ Erythematous psoriatic plaques, which are predominantly in the intertriginous areas or skin folds (inguinal, perineal, genital, intergluteal, axillary, or inframammary), are known as inverse psoriasis.

A psoriasis diagnosis is made by taking a history and a physical examination. Rarely, a skin biopsy of the lesions will be required for an atypical presentation. The course of the disease is unpredictable, variable, and dependent on the type of psoriasis. Psoriasis vulgaris is a chronic condition, whereas guttate psoriasis is often self-limited.⁴ A poorer prognosis is seen in patients with erythrodermic and generalized pustular psoriasis.⁴

Psoriatic Arthritis Presentation, Classification, and Diagnosis

Prevalence of PsA is not known, but it is estimated to be from 0.3% to 1% of the U.S. population. In the psoriasis population, PsA is reported to range from 7% to 42%,³ although more recently, these numbers have been found to be in the 15% to 25% range (unpublished observations). This type of inflammatory arthritis can develop at any age but usually is seen between the ages of 30 and 50 years, with men being affected equally or a little more than are women.³ Clinical symptoms usually include pain and stiffness of affected joints, > 30 minutes of morning stiffness, and fatigue.

The presentation of joint involvement can vary widely. Five subtypes of arthritis were identified by Moll and Wright in 1973, which included arthritis with predominant distal interphalangeal involvement, arthritis mutilans, symmetric polyarthritis (> 5 joints), asymmetric oligoarthritis (1-4 joints), and predominant spondylitis (axial).⁵ Patients with PsA may also have evidence of spondylitis (inflammation of vertebra) or sacroiliitis (inflammation of the sacroiliac joints) with back pain > 3 months, hip or buttock pain, nighttime pain, or pain that improves with activity but worsens with rest.6 The cervical spine is more frequently involved than is the lumbar spine in patients with PsA.³

Psoriatic arthritis can have a diverse presentation not only with the affected joints, but also involving nails, tendons, and ligaments. An entire digit of the hand or foot can become swollen, known as dactylitis, or “sausage digit.” Inflammation at the insertion of tendons or ligaments, known as enthesitis, is also seen in PsA. Most common sites include the Achilles tendon, plantar fascia, and ligamentous insertions around the pelvic bones.³ Nail changes that are typically seen in patients with psoriasis can be seen in PsA as well, including pitting, ridging, hyperkeratosis, and onycholysis.³ Ocular inflammation which is classically seen with other spondyloarthropathies, can be seen in patients with PsA as well, frequently manifesting as conjunctivitis.^2,3

Psoriatic arthritis is commonly classified under the broader category of seronegative spondyloarthropathies, given the low frequency of a positive rheumatoid factor.³ Currently, there are no laboratory tests that can help with a PsA diagnosis.³ Acute-phase reactants such as erythrocyte sedimentation rate and C-reactive protein may be elevated, indicating active inflammation.

Radiographic data, such as X-rays of the hands and feet, can confirm the clinical distribution of joint involvement and show evidence of erosive changes. Further destructive changes include osteolysis (bone resorption) that may cause the classic pencil-in-cup deformity, typically seen in arthritis mutilans (Figure 1).³ Other radiographic evidence of PsA can include proliferative changes with new bone formation seen along the shaft of the metacarpal and metatarsal bones.³ Patients with axial involvement can have evidence of asymmetric sacroiliitis, which can be seen on radiographs. Asymmetric syndesmophytes, or bony outgrowths, can also be seen throughout the axial spine.³

Diagnosis is based on the history and clinical presentation of a patient with the help of laboratory work and radiographs. Other forms of arthritis (such as rheumatoid arthritis, crystal arthropathies, osteoarthritis, ankylosing spondylitis) should be excluded. Given the varied presentation of PsA, classification criteria have been developed to assist in clinical research. Classification Criteria for Psoriatic Arthritis (CASPAR) have been developed and validated as an adjunct to clinical diagnosis and a source for clinical research (Table 1).⁷ Musculoskeletal pain in patients with psoriasis can be due to causes other than PsA, such as osteoarthritis and gout. A close working relationship in a combined rheumatology/dermatology clinic is vital to providing optimal diagnostic and treatment care for patients with psoriasis and PsA.⁸

The etiology of PsA is currently unknown, although many genetic, environmental, and immunologic factors have been identified that play a role in the pathogenesis of the disease. In this setting, immunologically mediated processes that cause inflammation occur in the synovium of joints, enthesium, bone, and skin of patients with PsA.⁹ Studies have shown that activated T cells and T-cell–derived cytokines play an important role in cartilage degradation, joint damage, and stimulating bone resorption.⁹

One particular proinflammatory cytokine, tumor necrosis factor alpha (TNFα), has been the target for many treatment modalities for several years. With new and ongoing research into the PsA pathogenesis, other treatment options have been discovered, targeting different cytokines and T cells that are involved in the disease process. This has led to drug trials and recent FDA approvals of several new medications, which provide further options for clinicians in managing and treating PsA.

Management of Psoriasis

Choice of therapy is determined by the extent and severity of psoriasis (body surface area [BSA] involvement) as well as the patient’s comorbidities and preferences.⁴ Providers have a wide spectrum of effective therapies to prescribe, both topically and systemically. Topical therapy options include corticosteroids, vitamin D3 and analogs (calcipotriene), anthralin, tar, tazarotene (third-generation retinoid), and calcineurin inhibitors (tacromlimus).⁴ Phototherapy with or without saltwater baths helps improve skin lesions.

These treatments are beneficial for all patients with psoriasis, but the disease can be controlled with monotherapy in patients with mild-to-moderate disease (< 10% BSA). Limiting these treatment options are some long-term effects of the medications because of the potential for toxicity as well as decreasing efficacy of the medication over time.4 For patients with more BSA involvement (> 10%), systemic treatment options include methotrexate (MTX), systemic retinoids (acitretin), calcineurin inhibitors (cyclosporine), and biologics. Many of these systemic treatment options overlap for patients with both psoriasis and PsA, and topical treatments can be used adjunctively to better control the skin disease.

Management of Psoriatic Arthritis

It is important to identify PsA and begin treatment early, because it has been shown that patients tend to fare better in their disease course if treated early.¹⁰ Once a diagnosis of PsA is made, disease activity needs to be determined by clinical examination and radiographs of joints. Scoring systems, by assessing bone erosions and deformities on joint radiographs, can aide with this assessment. Based on these, PsA can be categorized as mild, moderate, or severe. Several disease activity measures that have been developed for clinical trials in monitoring of disease activity can be used as an aide in the office setting. These tools are still being studied to determine the optimal measure of disease activity.

NSAIDs and Glucocorticoids

Controlling inflammation and providing pain relief are the primary treatment goals for patients with PsA. In mild, predominantly peripheral PsA, nonsteroidal antiinflammatory drugs (NSAIDs) can be used, but they do not halt disease progression. If the disease is controlled and not progressing, NSAIDs may be used as the only treatment. However, if symptoms persist and/or there is more joint involvement, the next level of therapy should be sought. Intra-articular corticosteroids for symptomatic relief can be given if only a few joints are affected. Oral corticosteroids can be used occasionally in patients with multiple joint aches, but they are typically avoided or tapered slowly to avoid worsening the patient’s skin psoriasis or having it evolve into a more severe form, such as pustular psoriasis.¹⁰ All these treatments can alleviate symptoms, but they do not prevent the progression of disease.

Disease-Modifying Antirheumatic Drugs

For patients who fail NSAIDs or present initially with more joint involvement (polyarthritis or > 5 swollen joints), traditional disease-modifying antirheumatic drugs (DMARDs) should be started (Table 2). Methotrexate is one of the first-line DMARD prescriptions. It is commonly used because of its effectiveness in treating both skin and joint involvement, despite limited evidence of its efficacy in controlled clinical trials for slowing the progression of joint damage in PsA.^2,9-11 Methotrexate can be given orally or subcutaneously (SC) every week. Routine laboratory monitoring is required given the known effects of MTX on liver and bone marrow suppression. Clinical monitoring is needed as well due to its well-known risk for pulmonary toxicity and teratogenicity.²

Leflunomide is another traditional oral DMARD that is administered daily. It has be shown to be effective in PsA, with only a modest effect in improving skin lesions.¹² Laboratory monitoring is identical to that required with MTX. Adverse effects (AEs) include diarrhea and increased risk of elevated transaminases.⁹ Sulfasalazine (SSZ) is also used as a traditional DMARD and shown to have an effective clinical response in treating peripheral arthritis but not in axial or skin disease.^9,12 Not all studies have shown effective responses to SSZ. The primary AE is gastrointestinal, making this a frequently discontinued medication.² Cyclosporine is more commonly used in psoriasis but can be used on its own or with MTX for treating patients with PsA.¹⁰ It is often not tolerated well and frequently discontinued, due to major AEs, including hypertension and renal dysfunction.^2,10

These traditional DMARDs are usually given for 3 to 6 months.¹³ After this initial period, the patient’s clinical response is reassessed, and the need for changing therapy to another DMARD or biologic is determined.

Biologic Therapies

With the discovery of TNFα as a potent cytokine in inflammatory arthritis came a new class of medications that has provided patients and providers with more effective treatment options. This category of medications is known as tumor necrosis factor inhibitors (TNFis). Five medications have been developed that target TNFα, each in its own way: etanercept, infliximab, adalimumab, golimumab, and certrolizumab pegol. These medications were initially studied in patients with rheumatoid arthritis, with further clinical trials performed for treatment of PsA. Each is prescribed differently: Adalimumab and certrolizumab are given SC every 2 weeks, etanercept is given weekly, and golimumab is given once a month. Infliximab is the only medication prescribed as an infusion, which is administered every 8 weeks after receiving 3 loading doses.

Studies have shown that all TNFis are effective in treating PsA: improving joint disease activity, inhibiting progression of structural damage, and improving function and overall quality of life^.10 The TNFi drugs also improve psoriasis along with dactylitis, enthesitis, and nail changes.¹³ Patients with
axial disease benefit from TNFi, but the evidence of TNFi effectiveness is extrapolated from studies in axial spondyloarthritis.^13,14 Tumor necrosis
factor inhibitors can be used as monotherapy, although there is some evidence for using TNFi drugs with MTX in PsA. Combination therapy can potentially prolong the survival of the TNFi drug or prevent formation of antidrug antibodies.^14,15

The current evidence for monotherapy vs combination therapy in patients with PsA is not consistent, and no formal guidelines have been developed to guide physicians one way or another. The TNFi drugs are generally well tolerated, although the patient needs to learn how to self-inject if given the SC route. Adverse effects include infusion or injection site reactions and infections. Prior to starting a TNFi, it is prudent to screen for latent tuberculosis infection as well as hepatitis B and C, given the risk of reactivation. Clinical response is monitored for 3 months, and if remission or low disease activity is not reached, a different TNFi may be tried.¹³ Importantly, patients receiving infliximab without clinical improvement in 3 months may have their dose and frequency increased before switching to an alternative TNFi. Some studies show that a trial of a second TNFi has a less potent response than with a first TNFi, and the drug survival is shorter in duration.¹³

One of the newest biologic agents approved for treating PsA is ustekinumab, a human monoclonal antibody (MAB) that inhibits receptor binding of cytokines interleukin (IL)-12 and IL-23. These cytokines have been identified in patients with psoriasis and PsA as further promoting inflammation. Ustekinumab recently received approval for the treatment of PsA and is given SC every 12 weeks after 2 initial doses. Further studies have also confirmed ustekinumab significantly suppressed radiographic progression of joint damage in patients with active PsA.¹⁵ Notable AEs included infections, but there have been no cases of tuberculosis or opportunistic infections reported.¹⁶

The most recent FDA-approved medication for PsA is apremilast. It is a phosphodiesterase-4 inhibitor, which causes the suppression of other proinflammatory mediators and cytokines active in the immune system.¹⁰ It is given orally, uptitrating the doses over a few days until the twice-daily maintenance dosing is achieved. It is generally well tolerated with nausea and diarrhea as the most common AEs.¹⁷ Further studies need to be conducted to assess whether this agent is able to prevent or decrease joint damage.

Other potential treatment options are currently undergoing trials to assess their efficacy and safety in treating psoriasis and/or PsA. One class targets the IL-17 cytokine pathway and includes brodalumab, a monoclonal antibody (MAB) anti-IL-17 receptor, ixekizumab and secukinumab, both MABs anti-IL-17A. Secukinumab has already received FDA approval for the treatment of plaque psoriasis (2015). Other agents currently undergoing trials are abatacept (cytotoxic T-lymphocyte antigen 4-Ig), a recombinant human fusion protein that blocks the co-stimulation of T cells9 and tofacitinib, a janus kinase inhibitor.¹⁸ Early studies show patients achieving a response with these medications, but further long-term studies are needed.¹⁹

Treatment Recommendations

Treatment approaches differ for patients with only psoriasis and patients with psoriasis and PsA, although some treatment modalities overlap. Recommendations for PsA have been set for each domain affected (Figure 2). The treatment approach is based on several factors, including severity or the degree of disease activity, any joint damage, and the patient’s comorbidities. Certain comorbidities are associated with PsA—cardiovascular disease, obesity, metabolic syndrome, diabetes, inflammatory bowel disease, fatty liver disease, chronic viral infections (hepatitis B or C), and kidney disease. These comorbidities can affect the choice of therapy for the patient.^20,21 Other factors affecting treatment choices include patient preference regarding mode and frequency of administration of the medication, potential AEs, requirements of laboratory monitoring or regular doctor visits, and the cost of medications.^10,22

In treating patients with psoriasis and PsA, a multidisciplinary approach is needed. Because skin manifestations of psoriasis usually develop prior to arthritis symptoms in most patients, primary care providers and dermatologists can routinely screen patients for arthritis.¹⁰ Rheumatologists can confirm arthritis and musculoskeletal involvement, but the treatment and management of these patients will need to be in collaboration with a dermatologist. The goal of comanagement is to choose appropriate therapies that may be able to treat both the skin and musculoskeletal manifestations.

A multidisciplinary approach can also limit polypharmacy, control costs, and reduce AEs. The existence of VA combined rheumatology and dermatology clinics makes this an invaluable experience for the veteran with direct and focused patient management. In addition to controlling disease activity, the goal of treatment is to improve function and the patient’s quality of life, halting structural joint damage to prevent disability.¹⁰ Physical and occupational therapies play an important role in PsA management as does exercise. Patients should be educated about their disease and treatment options discussed. It is also important to identify and reduce significant comorbidities, such as cardiovascular disease, to decrease mortality and improve life expectancy.¹⁰

Conclusion

Psoriasis is a distinct disease entity but can occur along with extracutaneous features. Patients with psoriasis need to be screened for PsA, and it is important to diagnose PsA early to begin appropriate treatment. Disease activity, severity, and any joint damage will determine therapy. Over the past decade, new treatment options have become available that provide more choices for patients than those of the standard DMARDs. The TNFis have proven to be efficacious in treating psoriasis and PsA. With a better understanding of pathogenesis of these diseases, new medications have been discovered targeting different parts of the immune system involved in dysregulation and ultimately inflammation. Additional clinical research is needed to provide physicians with more effective ways of controlling these diseases. Ultimately, the management of PsA is not solely based on medications, but the authors’ VA experience highlights the importance of a multispecialty approach to the management of psoriasis and PsA.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects— before administering pharmacologic therapy to patients.

Over the past 2 decades, an increasing number of rheumatologists have progressively incorporated ultrasound (US) as an invaluable diagnostic and monitoring tool into their clinical and research practice.^1,2 This imaging modality has become an established aid incorporated into the clinical evaluation of periarticular and articular structures involved in the diagnosis of several rheumatic disorders.

Ultrasound is a safe, noninvasive, patient-friendly imaging modality with a lack of contraindications and free of ionizing radiation. It allows real-time evaluation with dynamic assessment in a multiplanar view, assessment of multiple targets, and lower cost compared with magnetic resonance imaging (MRI) or computerized tomography scan. Above all, for the rheumatologist, US provides real-time scanning of all peripheral joints as many times as is required at the time of consultation. It is of great advantage in the assessment of a wide spectrum of abnormalities in rheumatic diseases with the potential of point-of-care imaging modality in the clinical evaluation and management of the patient. It facilitates a direct correlation between imaging findings and clinical data that improves the approach to a wide range of rheumatic diseases, from acute to chronic inflammatory arthritis, crystalline arthropathies, osteoarthritis (OA), spondyloarthropathies (SpA), vasculitis, and soft tissue syndromes. In addition, US is a bedside tool for performing accurate and safe diagnostic arthrocentesis, injections, and synovial biopsies.^3,4

Recently, a gradual attempt has been made to incorporate US into rheumatology disease classification or diagnostic criteria for rheumatoid arthritis (RA), polymyalgia rheumatica, gout, calcium pyrophosphate deposition disease (CPPD), and Sjögren’s syndrome.^5-10 Furthermore, the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) have produced evidence and expert opinion-based recommendations on the use of US in the clinical management of rheumatic diseases.^10-12 This article highlights the most common applications of US for assessment and management of different rheumatic diseases frequently encountered at the VAMC rheumatology inpatient and outpatient clinical service.

Evaluation of Inflammatory Arthritis

In RA and any other inflammatory arthritis, US has been used for the detection of joint effusions, synovitis, bone erosions, and tendon and enthesis involvement.^11,12 Ultrasound B-mode and power Doppler (PD) techniques have demonstrated a consistent and relevant role in optimizing the diagnosis, assessing the inflammatory activity, monitoring response to therapy, and predicting the inflammatory arthritis outcomes (Figures 1-3).^10-12 Ultrasound provides real-time information about the status of the synovial membrane, tendons, cartilage, bursae, and cortical bones, allowing an accurate assessment of the degree of inflammatory process in periarticular and articular tissues. Also, US can provide details about the characteristics of the collected fluid (ie, effusion or synovial hypertrophy), which is fundamental for the correct interpretation of the pathologic joint and/or soft tissue processes. The inflammatory process can be assessed by using PD mode, which detects and quantifies the vascular changes in the pannus due to vasodilation and the increased blood flow characteristic of active inflammation.^13,14

The Outcomes Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) study group developed standardized sonopathologic definitions and scanning methods to be used in the daily rheumatologic practice and clinical trials (Table 1).¹⁵ Furthermore, it developed a semiquantitative scale to assess the degree of synovitis in US B-mode and PD mode (Table 2).¹⁵

The use of US to find subclinical synovitis in patients with RA considered to be in clinical remission is a new issue.¹⁶ Some reports have demonstrated progressive joint damage in these patients with evidence of active inflammation on PDUS despite clinical remission.^17,18 More prospective studies are required to provide a better understanding of the long-term effects of residual inflammation and the proper long-term treatment of these patients. Furthermore, the PD signal has been shown to be superior to the Disease Activity Score 28 (DAS-28) in evaluating disease activity, particularly in predicting joint damage.¹⁸

Ultrasound may be considered the gold standard imaging tool for the assessment of tendons in inflammatory arthritis and includes the detection of tenosynovitis and anatomical damage represented by the loss of the normal fibrillar echotexture and loss of definition of the tendon margins, which may occur in early disease.^19,20 Tenosynovitis of the extensor carpi ulnaris (ECU) detected by US has been shown to be an independent predictive factor of erosive joint damage, suggesting that ECU tenosynovitis represents a useful ultrasonographic landmark in the diagnosis of early RA.²¹

The availability of new nonbiologic and biologic therapies for inflammatory arthritis has raised the importance of identifying early changes, such as the detection of early erosions, which portend a poor long-term prognosis. The capability of US in identifying this lesion at an earlier stage compared with conventional radiography (CR) has allowed the early diagnosis and treatment of these patients before irreversible joint destruction occurs.²² In spite of all the supportive evidence of US utility in RA, it is not considered among the mandatory diagnostic criteria in the ACR/EULAR classification criteria for RA.⁵ Still, the addition of US findings to these criteria has increased the number of patients who fulfilled the 1987 ACR classification criteria for RA after 18 months of follow-up.²³ Despite extensive evidence of its utility in the diagnosis and monitoring of RA, further studies are still needed.

Spondyloarthritis

Similar to RA, SpA discloses sonographic findings of inflammatory arthritis; however, with more entheseal and tenosynovium involvement. Ultrasound has also been used in the early identification of characteristic changes of the skin and nail tissues, which can aid the global assessment of this heterogeneous disease, especially in psoriatic arthritis (PsA). The most common locations of enthesitis in SpA are the quadriceps and the Achilles enthesis.^24,25

Although US offers detailed imaging for the assessment of both tendons and enthesis, there is a lack of literature evaluating dactylitis. The OMERACT group recently released a composite measure of activity and severity of US dactylitis, which included newly defined elementary US lesions that may discern dactylitis of a digit.^26,27 Ultrasound has been compared with MRI in the detection of SpA-related synovitis of the hands and feet and has demonstrated competitive diagnostic sensitivity.²⁸ Ultrasound also shows higher sensitivity in detecting synovitis of the hands and feet compared with clinical examination and CR in PsA.^28,29 Unfortunately, there are no strongly validated US findings that can aid in the differential diagnosis of PsA against other chronic inflammatory arthritides. The presence of peritendinous extensor tendon inflammation was a highly specific sonographic feature of PsA, because it was present in 66% of metacarpophalangeal (MCP) joints as the only US sign of inflammation compared with patients with RA.³⁰

Another application of US is in the evaluation of subclinical inflammation at the enthesis in patients with a history of psoriasis without prior history of PsA.^27,31 In those patients with psoriatic nail changes, more subclinical enthesitis was found compared with patients with psoriasis without nail involvement.³² Furthermore, subclinical joint inflammation has also been described.³³ These findings suggest a possible predictive value in patients with psoriasis who should be monitored on a regular basis, because they are at risk of developing PsA.

Subclinical enthesitis by US imaging has been described in patients with recurrent anterior uveitis and inflammatory bowel disease.^34,35 In cases where SpA is suspected but diagnostic criteria are not fulfilled, the presence of one enthesis with increased PD signal highly predicts the eventual development of SpA.³⁶ Therefore, B-mode and PD evaluations of the entheses are critical in the identification of patients who are at an increased risk of developing SpA.³⁷ Treatment monitoring is performed by using a US scoring system in a follow-up evaluation of patients with PsA. Some of the scoring systems have evaluated changes in B-mode US lesions (enthesis and soft tissues, such as skin and nails), whereas others focus on changes in the PD signal.^37,38

The Five Targets Power Doppler for Psoriatic Disease PD scoring system comprises the assessment of PD signal in the joint, tendon with synovial sheath, enthesis, skin, and nails. Each of the targets is scored from 0 to 3 points, with a maximum of 15 total points. Some studies have shown that PDUS can provide valuable information in the evaluation of psoriatic plaques and onychopathy in patients with psoriasis and PsA.³⁹ The detection of a PD signal within the dermis and nail bed is equivalent to active inflammation in these sites.^39-41 However, further studies with larger cohorts proving inter- and intra-observer reliability are necessary to consolidate these findings and comfortably apply them in clinical practice.

Osteoarthritis

Increasingly US is studied for its validity and reliability in evaluating periarticular soft tissue and cartilage changes in knee OA. The associated US findings include a high prevalence of synovitis with a low prevalence of a PD signal, the presence of osteophytes, and joint space narrowing.^42,43 Increased PD signal, synovial hypertrophy, and joint effusion were observed in patients with radiographically erosive OA compared with those with radiographically nonerosive OA.⁴⁴

Bone erosions and inflammatory changes are also frequently detected by US in both erosive and nodal hand OA.⁴⁵ Compared with MRI, US has shown a good to excellent correlation in the assessment of osteophytes, bone erosions, synovitis, and tenosynovitis in erosive and hand nodal OA.⁴⁶ In comparison with CR, US has shown to have a higher sensitivity in the assessment of bony erosions, osteophytes, and space narrowing.⁴⁷ Ultrasound is able to detect changes in the earlier stages of cartilage erosion in OA, characterized by loss of the sharp contour and variations in the echogenicity of the cartilage matrix, asymmetric shrinkage, and ultimately the disappearance of the cartilaginous band, which is more evident in the later stages of OA.⁴⁵

Similar to RA management, US has been used to monitor disease activity and response to OA treatment. Patients who received intra-articular hyaluronic acid or intramuscular methylprednisolone for OA treatment were found to have a decrease of PD signal intensity and synovial effusion posttreatment.48 One could extrapolate these findings and conclude that US could be an additional tool for monitoring disease activity and assessing response to local and systemic treatments in OA.

Crystalline Arthropathies

Ultrasound application to crystal diseases facilitates the identification of microcrystalline deposits within the synovial membrane (joints), cartilage (both hyaline cartilage and fibrocartilage), and periarticular tissues (tendons, bursae, and soft tissues). Crystals appear as hyperechogenic spots of different sizes and shapes that can be seen in both articular and periarticular tissues.^49,50 The crystal deposition pattern on hyaline cartilage allows the differentiation between monosodium urate (MSU) and calcium pyrophosphate dehydrate (CPP) crystals. The MSU crystals are deposited at the chondrosynovial (or superficial) margin of the hyaline cartilage and described sonographically as the double contour sign in gout, whereas CPP crystals are deposited within the intermediate layer of the hyaline cartilage and are seen as hyperechoic spots frequently described as rosary beads on US.^6,49,50

Other important sites that can be evaluated to determine the presence of CPP crystals include the menisci, symphysis pubis, and triangular fibrocartilage at the wrists, hips, and shoulders. Recent EULAR recommendations have incorporated US as part of the diagnostic imaging modality for the diagnosis of CPPD and more recently for gout.^6,51 Tophi are seen as MSU precipitates deposited in the joint cavity, tendons, and/or periarticular tissues such as bursae. They can show different echogenic signal. Soft tophi can demonstrate high PD signal due to high vascularization. On the other hand, hard tophi are hyperechoic on B-mode due to the presence of calcification, which does not allow passage of US waves, creating postacoustic shadowing.⁸ Studies have evaluated the predictive role of US in evaluating patients with asymptomatic hyperuricemia without any prior history of crystal-related joint disease and found tophaceous deposits in the triceps and patellar and quadriceps tendons.^52-55 Studies have also looked at using US in the assessment of treatment response to serum uratelowering therapy in patients with gout.^56,57 These studies have noted an improvement in the double contour sign, hyperechoic spots, cloudy areas in the synovial fluid, and tophus diameter and size in those patients who achieved a treat-to-target with a serum uric acid level ≤ 6 mg/dL. Patients who did not reach this target had no changes in the gout US features.^56-57 Larger cohort studies are needed to confirm these findings.

An active inflammatory process can be determined by using a PD signal in the acute gout setting with increased vascularization; however, an increased PD signal can also be seen in septic arthritis or tenosynovitis, which sometimes can coexist with crystal-induced arthritis. Therefore, diagnostic arthrocentesis, Gram stain, and culture, as well as evaluation of crystals under polarized microscopy, are still recommended.

Therapeutic Interventions

Real-time visualization of the injection needle by US allows reliable placement of the needle tip in the tissue or cavity of interest. Multiple studies have shown the low accuracy of palpation-guided injection for reaching the site of interest.^58,59 Some studies have shown a higher response rate to US-guided injections compared with palpation-guided as well as a higher rate of successful aspirations and clinical outcomes. Meta-analyses have demonstrated improved treatment response with the use of US-guided procedures compared with blinded injections.^60,61 Ultrasound-guided interventions are performed in both peripheral and axial joints.⁶² The most common US-guided procedures at the VA rheumatology clinic include arthrocentesis and intra-articular corticosteroid injections of small and medium-sized joints, such as MCP joints, elbows, wrists, and ankles.

Conclusions

Ultrasound is becoming a relevant part of rheumatology practice and research and can be regarded as a feasible and effective imaging technique that can allow real-time recognition of early anatomical changes, provide careful guidance for aspiration, and monitor local and/or systemic treatment response at the joint, tendon, enthesis, nail, and skin levels. Ultrasound is a user-friendly imaging modality readily applied at the bedside and considered an extension of the rheumatologist's physical examination.

The success of US depends on the individual operator. For this reason, structured educational programs during fellowship training programs and an efficient competency assessment system would facilitate proper implementation of US in rheumatology practice as performed by some but not all institutions.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Over the past 2 decades, an increasing number of rheumatologists have progressively incorporated ultrasound (US) as an invaluable diagnostic and monitoring tool into their clinical and research practice.^1,2 This imaging modality has become an established aid incorporated into the clinical evaluation of periarticular and articular structures involved in the diagnosis of several rheumatic disorders.

Ultrasound is a safe, noninvasive, patient-friendly imaging modality with a lack of contraindications and free of ionizing radiation. It allows real-time evaluation with dynamic assessment in a multiplanar view, assessment of multiple targets, and lower cost compared with magnetic resonance imaging (MRI) or computerized tomography scan. Above all, for the rheumatologist, US provides real-time scanning of all peripheral joints as many times as is required at the time of consultation. It is of great advantage in the assessment of a wide spectrum of abnormalities in rheumatic diseases with the potential of point-of-care imaging modality in the clinical evaluation and management of the patient. It facilitates a direct correlation between imaging findings and clinical data that improves the approach to a wide range of rheumatic diseases, from acute to chronic inflammatory arthritis, crystalline arthropathies, osteoarthritis (OA), spondyloarthropathies (SpA), vasculitis, and soft tissue syndromes. In addition, US is a bedside tool for performing accurate and safe diagnostic arthrocentesis, injections, and synovial biopsies.^3,4

Recently, a gradual attempt has been made to incorporate US into rheumatology disease classification or diagnostic criteria for rheumatoid arthritis (RA), polymyalgia rheumatica, gout, calcium pyrophosphate deposition disease (CPPD), and Sjögren’s syndrome.^5-10 Furthermore, the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) have produced evidence and expert opinion-based recommendations on the use of US in the clinical management of rheumatic diseases.^10-12 This article highlights the most common applications of US for assessment and management of different rheumatic diseases frequently encountered at the VAMC rheumatology inpatient and outpatient clinical service.

Evaluation of Inflammatory Arthritis

In RA and any other inflammatory arthritis, US has been used for the detection of joint effusions, synovitis, bone erosions, and tendon and enthesis involvement.^11,12 Ultrasound B-mode and power Doppler (PD) techniques have demonstrated a consistent and relevant role in optimizing the diagnosis, assessing the inflammatory activity, monitoring response to therapy, and predicting the inflammatory arthritis outcomes (Figures 1-3).^10-12 Ultrasound provides real-time information about the status of the synovial membrane, tendons, cartilage, bursae, and cortical bones, allowing an accurate assessment of the degree of inflammatory process in periarticular and articular tissues. Also, US can provide details about the characteristics of the collected fluid (ie, effusion or synovial hypertrophy), which is fundamental for the correct interpretation of the pathologic joint and/or soft tissue processes. The inflammatory process can be assessed by using PD mode, which detects and quantifies the vascular changes in the pannus due to vasodilation and the increased blood flow characteristic of active inflammation.^13,14

The Outcomes Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) study group developed standardized sonopathologic definitions and scanning methods to be used in the daily rheumatologic practice and clinical trials (Table 1).¹⁵ Furthermore, it developed a semiquantitative scale to assess the degree of synovitis in US B-mode and PD mode (Table 2).¹⁵

The use of US to find subclinical synovitis in patients with RA considered to be in clinical remission is a new issue.¹⁶ Some reports have demonstrated progressive joint damage in these patients with evidence of active inflammation on PDUS despite clinical remission.^17,18 More prospective studies are required to provide a better understanding of the long-term effects of residual inflammation and the proper long-term treatment of these patients. Furthermore, the PD signal has been shown to be superior to the Disease Activity Score 28 (DAS-28) in evaluating disease activity, particularly in predicting joint damage.¹⁸

Ultrasound may be considered the gold standard imaging tool for the assessment of tendons in inflammatory arthritis and includes the detection of tenosynovitis and anatomical damage represented by the loss of the normal fibrillar echotexture and loss of definition of the tendon margins, which may occur in early disease.^19,20 Tenosynovitis of the extensor carpi ulnaris (ECU) detected by US has been shown to be an independent predictive factor of erosive joint damage, suggesting that ECU tenosynovitis represents a useful ultrasonographic landmark in the diagnosis of early RA.²¹

The availability of new nonbiologic and biologic therapies for inflammatory arthritis has raised the importance of identifying early changes, such as the detection of early erosions, which portend a poor long-term prognosis. The capability of US in identifying this lesion at an earlier stage compared with conventional radiography (CR) has allowed the early diagnosis and treatment of these patients before irreversible joint destruction occurs.²² In spite of all the supportive evidence of US utility in RA, it is not considered among the mandatory diagnostic criteria in the ACR/EULAR classification criteria for RA.⁵ Still, the addition of US findings to these criteria has increased the number of patients who fulfilled the 1987 ACR classification criteria for RA after 18 months of follow-up.²³ Despite extensive evidence of its utility in the diagnosis and monitoring of RA, further studies are still needed.

Spondyloarthritis

Similar to RA, SpA discloses sonographic findings of inflammatory arthritis; however, with more entheseal and tenosynovium involvement. Ultrasound has also been used in the early identification of characteristic changes of the skin and nail tissues, which can aid the global assessment of this heterogeneous disease, especially in psoriatic arthritis (PsA). The most common locations of enthesitis in SpA are the quadriceps and the Achilles enthesis.^24,25

Although US offers detailed imaging for the assessment of both tendons and enthesis, there is a lack of literature evaluating dactylitis. The OMERACT group recently released a composite measure of activity and severity of US dactylitis, which included newly defined elementary US lesions that may discern dactylitis of a digit.^26,27 Ultrasound has been compared with MRI in the detection of SpA-related synovitis of the hands and feet and has demonstrated competitive diagnostic sensitivity.²⁸ Ultrasound also shows higher sensitivity in detecting synovitis of the hands and feet compared with clinical examination and CR in PsA.^28,29 Unfortunately, there are no strongly validated US findings that can aid in the differential diagnosis of PsA against other chronic inflammatory arthritides. The presence of peritendinous extensor tendon inflammation was a highly specific sonographic feature of PsA, because it was present in 66% of metacarpophalangeal (MCP) joints as the only US sign of inflammation compared with patients with RA.³⁰

Another application of US is in the evaluation of subclinical inflammation at the enthesis in patients with a history of psoriasis without prior history of PsA.^27,31 In those patients with psoriatic nail changes, more subclinical enthesitis was found compared with patients with psoriasis without nail involvement.³² Furthermore, subclinical joint inflammation has also been described.³³ These findings suggest a possible predictive value in patients with psoriasis who should be monitored on a regular basis, because they are at risk of developing PsA.

Subclinical enthesitis by US imaging has been described in patients with recurrent anterior uveitis and inflammatory bowel disease.^34,35 In cases where SpA is suspected but diagnostic criteria are not fulfilled, the presence of one enthesis with increased PD signal highly predicts the eventual development of SpA.³⁶ Therefore, B-mode and PD evaluations of the entheses are critical in the identification of patients who are at an increased risk of developing SpA.³⁷ Treatment monitoring is performed by using a US scoring system in a follow-up evaluation of patients with PsA. Some of the scoring systems have evaluated changes in B-mode US lesions (enthesis and soft tissues, such as skin and nails), whereas others focus on changes in the PD signal.^37,38

The Five Targets Power Doppler for Psoriatic Disease PD scoring system comprises the assessment of PD signal in the joint, tendon with synovial sheath, enthesis, skin, and nails. Each of the targets is scored from 0 to 3 points, with a maximum of 15 total points. Some studies have shown that PDUS can provide valuable information in the evaluation of psoriatic plaques and onychopathy in patients with psoriasis and PsA.³⁹ The detection of a PD signal within the dermis and nail bed is equivalent to active inflammation in these sites.^39-41 However, further studies with larger cohorts proving inter- and intra-observer reliability are necessary to consolidate these findings and comfortably apply them in clinical practice.

Osteoarthritis

Increasingly US is studied for its validity and reliability in evaluating periarticular soft tissue and cartilage changes in knee OA. The associated US findings include a high prevalence of synovitis with a low prevalence of a PD signal, the presence of osteophytes, and joint space narrowing.^42,43 Increased PD signal, synovial hypertrophy, and joint effusion were observed in patients with radiographically erosive OA compared with those with radiographically nonerosive OA.⁴⁴

Bone erosions and inflammatory changes are also frequently detected by US in both erosive and nodal hand OA.⁴⁵ Compared with MRI, US has shown a good to excellent correlation in the assessment of osteophytes, bone erosions, synovitis, and tenosynovitis in erosive and hand nodal OA.⁴⁶ In comparison with CR, US has shown to have a higher sensitivity in the assessment of bony erosions, osteophytes, and space narrowing.⁴⁷ Ultrasound is able to detect changes in the earlier stages of cartilage erosion in OA, characterized by loss of the sharp contour and variations in the echogenicity of the cartilage matrix, asymmetric shrinkage, and ultimately the disappearance of the cartilaginous band, which is more evident in the later stages of OA.⁴⁵

Similar to RA management, US has been used to monitor disease activity and response to OA treatment. Patients who received intra-articular hyaluronic acid or intramuscular methylprednisolone for OA treatment were found to have a decrease of PD signal intensity and synovial effusion posttreatment.48 One could extrapolate these findings and conclude that US could be an additional tool for monitoring disease activity and assessing response to local and systemic treatments in OA.

Crystalline Arthropathies

Ultrasound application to crystal diseases facilitates the identification of microcrystalline deposits within the synovial membrane (joints), cartilage (both hyaline cartilage and fibrocartilage), and periarticular tissues (tendons, bursae, and soft tissues). Crystals appear as hyperechogenic spots of different sizes and shapes that can be seen in both articular and periarticular tissues.^49,50 The crystal deposition pattern on hyaline cartilage allows the differentiation between monosodium urate (MSU) and calcium pyrophosphate dehydrate (CPP) crystals. The MSU crystals are deposited at the chondrosynovial (or superficial) margin of the hyaline cartilage and described sonographically as the double contour sign in gout, whereas CPP crystals are deposited within the intermediate layer of the hyaline cartilage and are seen as hyperechoic spots frequently described as rosary beads on US.^6,49,50

Other important sites that can be evaluated to determine the presence of CPP crystals include the menisci, symphysis pubis, and triangular fibrocartilage at the wrists, hips, and shoulders. Recent EULAR recommendations have incorporated US as part of the diagnostic imaging modality for the diagnosis of CPPD and more recently for gout.^6,51 Tophi are seen as MSU precipitates deposited in the joint cavity, tendons, and/or periarticular tissues such as bursae. They can show different echogenic signal. Soft tophi can demonstrate high PD signal due to high vascularization. On the other hand, hard tophi are hyperechoic on B-mode due to the presence of calcification, which does not allow passage of US waves, creating postacoustic shadowing.⁸ Studies have evaluated the predictive role of US in evaluating patients with asymptomatic hyperuricemia without any prior history of crystal-related joint disease and found tophaceous deposits in the triceps and patellar and quadriceps tendons.^52-55 Studies have also looked at using US in the assessment of treatment response to serum uratelowering therapy in patients with gout.^56,57 These studies have noted an improvement in the double contour sign, hyperechoic spots, cloudy areas in the synovial fluid, and tophus diameter and size in those patients who achieved a treat-to-target with a serum uric acid level ≤ 6 mg/dL. Patients who did not reach this target had no changes in the gout US features.^56-57 Larger cohort studies are needed to confirm these findings.

An active inflammatory process can be determined by using a PD signal in the acute gout setting with increased vascularization; however, an increased PD signal can also be seen in septic arthritis or tenosynovitis, which sometimes can coexist with crystal-induced arthritis. Therefore, diagnostic arthrocentesis, Gram stain, and culture, as well as evaluation of crystals under polarized microscopy, are still recommended.

Therapeutic Interventions

Real-time visualization of the injection needle by US allows reliable placement of the needle tip in the tissue or cavity of interest. Multiple studies have shown the low accuracy of palpation-guided injection for reaching the site of interest.^58,59 Some studies have shown a higher response rate to US-guided injections compared with palpation-guided as well as a higher rate of successful aspirations and clinical outcomes. Meta-analyses have demonstrated improved treatment response with the use of US-guided procedures compared with blinded injections.^60,61 Ultrasound-guided interventions are performed in both peripheral and axial joints.⁶² The most common US-guided procedures at the VA rheumatology clinic include arthrocentesis and intra-articular corticosteroid injections of small and medium-sized joints, such as MCP joints, elbows, wrists, and ankles.

Conclusions

Ultrasound is becoming a relevant part of rheumatology practice and research and can be regarded as a feasible and effective imaging technique that can allow real-time recognition of early anatomical changes, provide careful guidance for aspiration, and monitor local and/or systemic treatment response at the joint, tendon, enthesis, nail, and skin levels. Ultrasound is a user-friendly imaging modality readily applied at the bedside and considered an extension of the rheumatologist's physical examination.

The success of US depends on the individual operator. For this reason, structured educational programs during fellowship training programs and an efficient competency assessment system would facilitate proper implementation of US in rheumatology practice as performed by some but not all institutions.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.

Over the past 2 decades, an increasing number of rheumatologists have progressively incorporated ultrasound (US) as an invaluable diagnostic and monitoring tool into their clinical and research practice.^1,2 This imaging modality has become an established aid incorporated into the clinical evaluation of periarticular and articular structures involved in the diagnosis of several rheumatic disorders.

Ultrasound is a safe, noninvasive, patient-friendly imaging modality with a lack of contraindications and free of ionizing radiation. It allows real-time evaluation with dynamic assessment in a multiplanar view, assessment of multiple targets, and lower cost compared with magnetic resonance imaging (MRI) or computerized tomography scan. Above all, for the rheumatologist, US provides real-time scanning of all peripheral joints as many times as is required at the time of consultation. It is of great advantage in the assessment of a wide spectrum of abnormalities in rheumatic diseases with the potential of point-of-care imaging modality in the clinical evaluation and management of the patient. It facilitates a direct correlation between imaging findings and clinical data that improves the approach to a wide range of rheumatic diseases, from acute to chronic inflammatory arthritis, crystalline arthropathies, osteoarthritis (OA), spondyloarthropathies (SpA), vasculitis, and soft tissue syndromes. In addition, US is a bedside tool for performing accurate and safe diagnostic arthrocentesis, injections, and synovial biopsies.^3,4

Recently, a gradual attempt has been made to incorporate US into rheumatology disease classification or diagnostic criteria for rheumatoid arthritis (RA), polymyalgia rheumatica, gout, calcium pyrophosphate deposition disease (CPPD), and Sjögren’s syndrome.^5-10 Furthermore, the American College of Rheumatology (ACR) and the European League Against Rheumatism (EULAR) have produced evidence and expert opinion-based recommendations on the use of US in the clinical management of rheumatic diseases.^10-12 This article highlights the most common applications of US for assessment and management of different rheumatic diseases frequently encountered at the VAMC rheumatology inpatient and outpatient clinical service.

Evaluation of Inflammatory Arthritis

In RA and any other inflammatory arthritis, US has been used for the detection of joint effusions, synovitis, bone erosions, and tendon and enthesis involvement.^11,12 Ultrasound B-mode and power Doppler (PD) techniques have demonstrated a consistent and relevant role in optimizing the diagnosis, assessing the inflammatory activity, monitoring response to therapy, and predicting the inflammatory arthritis outcomes (Figures 1-3).^10-12 Ultrasound provides real-time information about the status of the synovial membrane, tendons, cartilage, bursae, and cortical bones, allowing an accurate assessment of the degree of inflammatory process in periarticular and articular tissues. Also, US can provide details about the characteristics of the collected fluid (ie, effusion or synovial hypertrophy), which is fundamental for the correct interpretation of the pathologic joint and/or soft tissue processes. The inflammatory process can be assessed by using PD mode, which detects and quantifies the vascular changes in the pannus due to vasodilation and the increased blood flow characteristic of active inflammation.^13,14

The Outcomes Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) study group developed standardized sonopathologic definitions and scanning methods to be used in the daily rheumatologic practice and clinical trials (Table 1).¹⁵ Furthermore, it developed a semiquantitative scale to assess the degree of synovitis in US B-mode and PD mode (Table 2).¹⁵

The use of US to find subclinical synovitis in patients with RA considered to be in clinical remission is a new issue.¹⁶ Some reports have demonstrated progressive joint damage in these patients with evidence of active inflammation on PDUS despite clinical remission.^17,18 More prospective studies are required to provide a better understanding of the long-term effects of residual inflammation and the proper long-term treatment of these patients. Furthermore, the PD signal has been shown to be superior to the Disease Activity Score 28 (DAS-28) in evaluating disease activity, particularly in predicting joint damage.¹⁸

Ultrasound may be considered the gold standard imaging tool for the assessment of tendons in inflammatory arthritis and includes the detection of tenosynovitis and anatomical damage represented by the loss of the normal fibrillar echotexture and loss of definition of the tendon margins, which may occur in early disease.^19,20 Tenosynovitis of the extensor carpi ulnaris (ECU) detected by US has been shown to be an independent predictive factor of erosive joint damage, suggesting that ECU tenosynovitis represents a useful ultrasonographic landmark in the diagnosis of early RA.²¹

The availability of new nonbiologic and biologic therapies for inflammatory arthritis has raised the importance of identifying early changes, such as the detection of early erosions, which portend a poor long-term prognosis. The capability of US in identifying this lesion at an earlier stage compared with conventional radiography (CR) has allowed the early diagnosis and treatment of these patients before irreversible joint destruction occurs.²² In spite of all the supportive evidence of US utility in RA, it is not considered among the mandatory diagnostic criteria in the ACR/EULAR classification criteria for RA.⁵ Still, the addition of US findings to these criteria has increased the number of patients who fulfilled the 1987 ACR classification criteria for RA after 18 months of follow-up.²³ Despite extensive evidence of its utility in the diagnosis and monitoring of RA, further studies are still needed.

Spondyloarthritis

Similar to RA, SpA discloses sonographic findings of inflammatory arthritis; however, with more entheseal and tenosynovium involvement. Ultrasound has also been used in the early identification of characteristic changes of the skin and nail tissues, which can aid the global assessment of this heterogeneous disease, especially in psoriatic arthritis (PsA). The most common locations of enthesitis in SpA are the quadriceps and the Achilles enthesis.^24,25

Although US offers detailed imaging for the assessment of both tendons and enthesis, there is a lack of literature evaluating dactylitis. The OMERACT group recently released a composite measure of activity and severity of US dactylitis, which included newly defined elementary US lesions that may discern dactylitis of a digit.^26,27 Ultrasound has been compared with MRI in the detection of SpA-related synovitis of the hands and feet and has demonstrated competitive diagnostic sensitivity.²⁸ Ultrasound also shows higher sensitivity in detecting synovitis of the hands and feet compared with clinical examination and CR in PsA.^28,29 Unfortunately, there are no strongly validated US findings that can aid in the differential diagnosis of PsA against other chronic inflammatory arthritides. The presence of peritendinous extensor tendon inflammation was a highly specific sonographic feature of PsA, because it was present in 66% of metacarpophalangeal (MCP) joints as the only US sign of inflammation compared with patients with RA.³⁰

Another application of US is in the evaluation of subclinical inflammation at the enthesis in patients with a history of psoriasis without prior history of PsA.^27,31 In those patients with psoriatic nail changes, more subclinical enthesitis was found compared with patients with psoriasis without nail involvement.³² Furthermore, subclinical joint inflammation has also been described.³³ These findings suggest a possible predictive value in patients with psoriasis who should be monitored on a regular basis, because they are at risk of developing PsA.

Subclinical enthesitis by US imaging has been described in patients with recurrent anterior uveitis and inflammatory bowel disease.^34,35 In cases where SpA is suspected but diagnostic criteria are not fulfilled, the presence of one enthesis with increased PD signal highly predicts the eventual development of SpA.³⁶ Therefore, B-mode and PD evaluations of the entheses are critical in the identification of patients who are at an increased risk of developing SpA.³⁷ Treatment monitoring is performed by using a US scoring system in a follow-up evaluation of patients with PsA. Some of the scoring systems have evaluated changes in B-mode US lesions (enthesis and soft tissues, such as skin and nails), whereas others focus on changes in the PD signal.^37,38

The Five Targets Power Doppler for Psoriatic Disease PD scoring system comprises the assessment of PD signal in the joint, tendon with synovial sheath, enthesis, skin, and nails. Each of the targets is scored from 0 to 3 points, with a maximum of 15 total points. Some studies have shown that PDUS can provide valuable information in the evaluation of psoriatic plaques and onychopathy in patients with psoriasis and PsA.³⁹ The detection of a PD signal within the dermis and nail bed is equivalent to active inflammation in these sites.^39-41 However, further studies with larger cohorts proving inter- and intra-observer reliability are necessary to consolidate these findings and comfortably apply them in clinical practice.

Osteoarthritis

Increasingly US is studied for its validity and reliability in evaluating periarticular soft tissue and cartilage changes in knee OA. The associated US findings include a high prevalence of synovitis with a low prevalence of a PD signal, the presence of osteophytes, and joint space narrowing.^42,43 Increased PD signal, synovial hypertrophy, and joint effusion were observed in patients with radiographically erosive OA compared with those with radiographically nonerosive OA.⁴⁴

Bone erosions and inflammatory changes are also frequently detected by US in both erosive and nodal hand OA.⁴⁵ Compared with MRI, US has shown a good to excellent correlation in the assessment of osteophytes, bone erosions, synovitis, and tenosynovitis in erosive and hand nodal OA.⁴⁶ In comparison with CR, US has shown to have a higher sensitivity in the assessment of bony erosions, osteophytes, and space narrowing.⁴⁷ Ultrasound is able to detect changes in the earlier stages of cartilage erosion in OA, characterized by loss of the sharp contour and variations in the echogenicity of the cartilage matrix, asymmetric shrinkage, and ultimately the disappearance of the cartilaginous band, which is more evident in the later stages of OA.⁴⁵

Similar to RA management, US has been used to monitor disease activity and response to OA treatment. Patients who received intra-articular hyaluronic acid or intramuscular methylprednisolone for OA treatment were found to have a decrease of PD signal intensity and synovial effusion posttreatment.48 One could extrapolate these findings and conclude that US could be an additional tool for monitoring disease activity and assessing response to local and systemic treatments in OA.

Crystalline Arthropathies

Ultrasound application to crystal diseases facilitates the identification of microcrystalline deposits within the synovial membrane (joints), cartilage (both hyaline cartilage and fibrocartilage), and periarticular tissues (tendons, bursae, and soft tissues). Crystals appear as hyperechogenic spots of different sizes and shapes that can be seen in both articular and periarticular tissues.^49,50 The crystal deposition pattern on hyaline cartilage allows the differentiation between monosodium urate (MSU) and calcium pyrophosphate dehydrate (CPP) crystals. The MSU crystals are deposited at the chondrosynovial (or superficial) margin of the hyaline cartilage and described sonographically as the double contour sign in gout, whereas CPP crystals are deposited within the intermediate layer of the hyaline cartilage and are seen as hyperechoic spots frequently described as rosary beads on US.^6,49,50

Other important sites that can be evaluated to determine the presence of CPP crystals include the menisci, symphysis pubis, and triangular fibrocartilage at the wrists, hips, and shoulders. Recent EULAR recommendations have incorporated US as part of the diagnostic imaging modality for the diagnosis of CPPD and more recently for gout.^6,51 Tophi are seen as MSU precipitates deposited in the joint cavity, tendons, and/or periarticular tissues such as bursae. They can show different echogenic signal. Soft tophi can demonstrate high PD signal due to high vascularization. On the other hand, hard tophi are hyperechoic on B-mode due to the presence of calcification, which does not allow passage of US waves, creating postacoustic shadowing.⁸ Studies have evaluated the predictive role of US in evaluating patients with asymptomatic hyperuricemia without any prior history of crystal-related joint disease and found tophaceous deposits in the triceps and patellar and quadriceps tendons.^52-55 Studies have also looked at using US in the assessment of treatment response to serum uratelowering therapy in patients with gout.^56,57 These studies have noted an improvement in the double contour sign, hyperechoic spots, cloudy areas in the synovial fluid, and tophus diameter and size in those patients who achieved a treat-to-target with a serum uric acid level ≤ 6 mg/dL. Patients who did not reach this target had no changes in the gout US features.^56-57 Larger cohort studies are needed to confirm these findings.

An active inflammatory process can be determined by using a PD signal in the acute gout setting with increased vascularization; however, an increased PD signal can also be seen in septic arthritis or tenosynovitis, which sometimes can coexist with crystal-induced arthritis. Therefore, diagnostic arthrocentesis, Gram stain, and culture, as well as evaluation of crystals under polarized microscopy, are still recommended.

Therapeutic Interventions

Real-time visualization of the injection needle by US allows reliable placement of the needle tip in the tissue or cavity of interest. Multiple studies have shown the low accuracy of palpation-guided injection for reaching the site of interest.^58,59 Some studies have shown a higher response rate to US-guided injections compared with palpation-guided as well as a higher rate of successful aspirations and clinical outcomes. Meta-analyses have demonstrated improved treatment response with the use of US-guided procedures compared with blinded injections.^60,61 Ultrasound-guided interventions are performed in both peripheral and axial joints.⁶² The most common US-guided procedures at the VA rheumatology clinic include arthrocentesis and intra-articular corticosteroid injections of small and medium-sized joints, such as MCP joints, elbows, wrists, and ankles.

Conclusions

Ultrasound is becoming a relevant part of rheumatology practice and research and can be regarded as a feasible and effective imaging technique that can allow real-time recognition of early anatomical changes, provide careful guidance for aspiration, and monitor local and/or systemic treatment response at the joint, tendon, enthesis, nail, and skin levels. Ultrasound is a user-friendly imaging modality readily applied at the bedside and considered an extension of the rheumatologist's physical examination.

The success of US depends on the individual operator. For this reason, structured educational programs during fellowship training programs and an efficient competency assessment system would facilitate proper implementation of US in rheumatology practice as performed by some but not all institutions.

Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.

Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review the complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.