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Flashcards in Chapter 08 Rheumatology Deck (19):
1

OSTEOARTHRITIS (OA), the most prevalent form of arthritis in the United States, is caused by a disruption of the normal process of degradation and synthesis of articular cartilage and __________ bone. Biomechanical and biologic factors are implicated. __________, __________, and __________ gender are among the risk factors; joint involvement is typically __________. Weight-bearing joints are usually involved.

OSTEOARTHRITIS (OA), the most prevalent form of arthritis in the United States, is caused by a disruption of the normal process of degradation and synthesis of articular cartilage and subchondral bone. Biomechanical and biologic factors are implicated. Age, obesity, and female gender are among the risk factors; joint involvement is typically asymmetric. Weight-bearing joints are usually involved.

2

OSTEOARTHRITIS: Characteristically, pain is worsened by joint use (__________ of day), and stiffness occurs with inactivity (__________). Classification criteria exist for OA of the hand, hip, and knee and include various combinations of clinical and radiologic features. Generally, evidence of pain at the specified joint, with bony swelling and lack of inflammatory markers (ESR __________, morning stiffness __________ minutes, __________, and __________ to touch) in a patient > 50 years, is a consistent feature of the disease. Radiologic confirmation on the basis of joint space narrowing and osteophyte formation can be made.

OSTEOARTHRITIS: Characteristically, pain is worsened by joint use (end of day), and stiffness occurs with inactivity (gelling). Classification criteria exist for OA of the hand, hip, and knee and include various combinations of clinical and radiologic features. Generally, evidence of pain at the specified joint, with bony swelling and lack of inflammatory markers (ESR 20, morning stiffness 30 minutes, nonerythematous, and cool to touch) in a patient > 50 years, is a consistent feature of the disease. Radiologic confirmation on the basis of joint space narrowing and osteophyte formation can be made.

3

OSTEOARTHRITIS: Nonpharmacologic Management
Strengthening and __________ exercises (e.g., fitness walking) have been shown in numerous trials to reduce pain and disability while improving quality of life. The FAST confirmed the beneficial effects of quadriceps strengthening and aerobic exercise in patients with knee OA. Felsen reported that a decrease of __________ BMI units (~__________ lbs) over 10 years in a group of women above median BMI decreased the odds of developing OA by over 50%. To promote self-efficacy, psychological well-being, and improved pain levels, patients should be encouraged to participate in programs such as the Arthritis Foundation Self-Help Course. For patients who are poorly tolerant of weight-bearing exercises due to their OA, aquatic exercises may be an alternative. (Swimming, however, may worsen lumbar facet arthritis symptoms.) Physical modalities and judicious rest between sessions may also improve tolerance and compliance with exercises.

OSTEOARTHRITIS: Nonpharmacologic Management
Strengthening and aerobic exercises (e.g., fitness walking) have been shown in numerous trials to reduce pain and disability while improving quality of life. The FAST confirmed the beneficial effects of quadriceps strengthening and aerobic exercise in patients with knee OA. Felsen reported that a decrease of 2 BMI units (~11.2 lbs) over 10 years in a group of women above median BMI decreased the odds of developing OA by over 50%. To promote self-efficacy, psychological well-being, and improved pain levels, patients should be encouraged to participate in programs such as the Arthritis Foundation Self-Help Course. For patients who are poorly tolerant of weight-bearing exercises due to their OA, aquatic exercises may be an alternative. (Swimming, however, may worsen lumbar facet arthritis symptoms.) Physical modalities and judicious rest between sessions may also improve tolerance and compliance with exercises.

4

OSTEOARTHRITIS
A cane held in the hand __________ to a painful hip can help unload the joint and make ambulation more bearable. For a painful knee, the cane can be held in either hand. Knee unloading __________ and __________ heel wedges can reduce stress in the medial knee compartment and relieve pain. Environmental adaptations include raising toilet and chair heights.

OSTEOARTHRITIS
A cane held in the hand contralateral to a painful hip can help unload the joint and make ambulation more bearable. For a painful knee, the cane can be held in either hand. Knee unloading braces and lateral heel wedges can reduce stress in the medial knee compartment and relieve pain. Environmental adaptations include raising toilet and chair heights.

5

OSTEOARTHRITIS: Pharmacologic Options, per ACR
Pharmaceutical agents are most effective when combined with nonpharmacologic strategies. A trial of __________ is recommended as the initial treatment for mild to moderate hip OA or knee OA without gross inflammation because of its overall cost, efficacy, and toxicity profile. For patients with moderate to severe knee OA and signs of joint inflammation, IA __________, __________-2 inhibitors, or __________ (with __________ or a proton pump inhibitor if the patient is at risk for adverse upper gastrointestinal events) may be considered as first-line therapy.

OSTEOARTHRITIS: Pharmacologic Options, per ACR
Pharmaceutical agents are most effective when combined with nonpharmacologic strategies. A trial of acetaminophen is recommended as the initial treatment for mild to moderate hip OA or knee OA without gross inflammation because of its overall cost, efficacy, and toxicity profile. For patients with moderate to severe knee OA and signs of joint inflammation, IA steroids, COX-2 inhibitors, or NSAIDs (with misoprostol or a proton pump inhibitor if the patient is at risk for adverse upper gastrointestinal events) may be considered as first-line therapy.

6

OSTEOARTHRITIS: Pharmacologic Options, per ACR
__________ can be considered in patients with moderate to severe pain with contraindications to NSAIDs/COX-2 agents and/or failing other treatments. The mean effective daily dose for __________ has generally been ~__________ to __________ mg, divided into four doses. More potent opioids can be considered for patients not tolerating or failing __________.

OSTEOARTHRITIS: Pharmacologic Options, per ACR
Tramadol can be considered in patients with moderate to severe pain with contraindications to NSAIDs/COX-2 agents and/or failing other treatments. The mean effective daily dose for tramadol has generally been ~200 to 300 mg, divided into four doses. More potent opioids can be considered for patients not tolerating or failing tramadol.

7

OSTEOARTHRITIS: Pharmacologic Options, per ACR
Topical analgesics (e.g., methyl salicylate or __________) can be considered in patients with mild to moderate knee OA pain as an adjunctive treatment or as monotherapy. Voltaren (__________) gel is also available to treat the pain of OA of both knees and hands; IA hyaluronan therapy (e.g., Synvisc) is indicated for patients with knee (not hip) OA with a poor response to simple analgesics and nonpharmacologic treatment. Studies of IA hyaluronan are somewhat controversial and inconclusive, but generally seem to favor its use in mild to moderate knee OA. Peak effects may be at 8 to 12 weeks; duration of action may be up to 6 months. Limited data are available regarding the efficacy of multiple courses of IA hyaluronan. IA glucocorticoids fluoroscopically guided into the hip joint may be efficacious in some patients.

OSTEOARTHRITIS: Pharmacologic Options, per ACR
Topical analgesics (e.g., methyl salicylate or capsaicin) can be considered in patients with mild to moderate knee OA pain as an adjunctive treatment or as monotherapy. Voltaren (diclofenac) gel is also available to treat the pain of OA of both knees and hands; IA hyaluronan therapy (e.g., Synvisc) is indicated for patients with knee (not hip) OA with a poor response to simple analgesics and nonpharmacologic treatment. Studies of IA hyaluronan are somewhat controversial and inconclusive, but generally seem to favor its use in mild to moderate knee OA. Peak effects may be at 8 to 12 weeks; duration of action may be up to 6 months. Limited data are available regarding the efficacy of multiple courses of IA hyaluronan. IA glucocorticoids fluoroscopically guided into the hip joint may be efficacious in some patients.

8

OSTEOARTHRITIS: Alternative and Investigational Treatments
Complementary and alternative medicine treatments abound. Although preliminary studies of glucosamine/chondroitin appeared promising at providing modest short-term symptomatic improvement, a recent NIH-sponsored multicenter trial (GAIT) did not show benefit in pain, function, or radiologic progression in over 1,500 patients with knee OA. Research on the efficacy of acupuncture in OA is likewise promising but qualitatively suboptimal. Other complementary treatments currently under investigation include supplementation with vitamin D and the antioxidant vitamins A, C, E, and coenzyme Q10, and curcumin- phosphatidylcholine.

OSTEOARTHRITIS: Alternative and Investigational Treatments
Complementary and alternative medicine treatments abound. Although preliminary studies of glucosamine/chondroitin appeared promising at providing modest short-term symptomatic improvement, a recent NIH-sponsored multicenter trial (GAIT) did not show benefit in pain, function, or radiologic progression in over 1,500 patients with knee OA. Research on the efficacy of acupuncture in OA is likewise promising but qualitatively suboptimal. Other complementary treatments currently under investigation include supplementation with vitamin D and the antioxidant vitamins A, C, E, and coenzyme Q10, and curcumin- phosphatidylcholine.

9

OSTEOARTHRITIS: Alternative and Investigational Treatments
A recent development in the surgical treatment of knee OA is the UniSpacer, which is FDA approved for isolated, moderate, __________ compartment OA. The kidney bean–shaped lightweight metallic alloy device is a self-centering bearing that requires no shaving of bone or screw/cement fixation to the native anatomy. Long-term efficacy is under investigation, though early clinical studies are disappointing with high revision rates and only modest relief of pain.

OSTEOARTHRITIS: Alternative and Investigational Treatments
A recent development in the surgical treatment of knee OA is the UniSpacer, which is FDA approved for isolated, moderate, medial compartment OA. The kidney bean–shaped lightweight metallic alloy device is a self-centering bearing that requires no shaving of bone or screw/cement fixation to the native anatomy. Long-term efficacy is under investigation, though early clinical studies are disappointing with high revision rates and only modest relief of pain.

10

OSTEOARTHRITIS: Alternative and Investigational Treatments
Greater understanding of chondrocyte biology and the inflammatory mediators of this disease has already led to novel investigational therapeutic targets, known as __________, e.g., iNOS inhibition, pentosan, and IA administration of autologous conditioned serum.

OSTEOARTHRITIS: Alternative and Investigational Treatments
Greater understanding of chondrocyte biology and the inflammatory mediators of this disease has already led to novel investigational therapeutic targets, known as DMOADs (disease modifying osteoarthritis drug), e.g., iNOS inhibition, pentosan, and IA administration of autologous conditioned serum.

11

RHEUMATOID ARTHRITIS
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder affecting women more than men, with ~1% prevalence in the United States. RA can cause an erosive, polyarticular, typically symmetric synovitis with or without extra-articular manifestations (fatigue, anemia, rheumatoid nodules, cardiac valve abnormalities, and pericarditis). Classic late physical examination findings include __________, __________ neck, or __________ finger deformities, __________ wrist swelling, __________ cysts, MCP subluxation with ulnar deviation of the fingers, and __________ joint sparing.
Modified ACR/EULAR classification criteria for the diagnosis of RA were introduced in 2010 and focus on early inflammatory disease parameters, rather than late-stage features. As a result, ACPA has been added, as have the acute phase reactants ESR and CRP, while the concept of symmetry has been greatly minimized and erosive disease eliminated from the tree algorithm.

RHEUMATOID ARTHRITIS
Rheumatoid arthritis (RA) is a chronic systemic inflammatory disorder affecting women more than men, with ~1% prevalence in the United States. RA can cause an erosive, polyarticular, typically symmetric synovitis with or without extra-articular manifestations (fatigue, anemia, rheumatoid nodules, cardiac valve abnormalities, and pericarditis). Classic late physical examination findings include boutonniere's, swan neck, or mallet finger deformities, symmetric wrist swelling, Baker's cysts, MCP subluxation with ulnar deviation of the fingers, and DIP joint sparing.
Modified ACR/EULAR classification criteria for the diagnosis of RA were introduced in 2010 and focus on early inflammatory disease parameters, rather than late-stage features. As a result, ACPA has been added, as have the acute phase reactants ESR and CRP, while the concept of symmetry has been greatly minimized and erosive disease eliminated from the tree algorithm.

12

RHEUMATOID ARTHRITIS Management
RA management must include both early pharmacologic therapy and nonpharmacologic interventions. __________ exercises and __________ should be regularly practiced. __________ strengthening exercises are preferred to minimize joint inflammation. Splints, particularly resting wrist-hand splints and knee or hindfoot splints, are helpful in reducing pain and preventing progression of deformity. A dorsal hand orthosis with an ulnar aspect MCP block and individual finger stops can be useful in the setting of ulnar deviation. Education should emphasize avoidance of overuse and joint protection techniques (e.g., decreasing activity during flare-ups, modifying activities to reduce joint stress, using splints, and maintaining strength).
Current treatment algorithms involve early institution of DMARDs and/or biologics and have allowed the primary target for treatment of RA to be a state of remission. Although NSAIDs, COX-2 inhibitors, and oral steroids may be helpful symptomatically in mild or early disease, they are currently used only as adjunctive therapy. DMARDs offer symptomatic relief, have been shown to modify disease progression, and are currently the first-line therapy in early RA, being initiated within 3 months of disease onset. Examples of currently used DMARDs include MTX, leflunomide, sulfasalazine, and hydroxychloroquine, although MTX is by far the most common and best tolerated.

RHEUMATOID ARTHRITIS Management
RA management must include both early pharmacologic therapy and nonpharmacologic interventions. ROM exercises and stretching should be regularly practiced. Isometric strengthening exercises are preferred to minimize joint inflammation. Splints, particularly resting wrist-hand splints and knee or hindfoot splints, are helpful in reducing pain and preventing progression of deformity. A dorsal hand orthosis with an ulnar aspect MCP block and individual finger stops can be useful in the setting of ulnar deviation. Education should emphasize avoidance of overuse and joint protection techniques (e.g., decreasing activity during flare-ups, modifying activities to reduce joint stress, using splints, and maintaining strength).
Current treatment algorithms involve early institution of DMARDs and/or biologics and have allowed the primary target for treatment of RA to be a state of remission. Although NSAIDs, COX-2 inhibitors, and oral steroids may be helpful symptomatically in mild or early disease, they are currently used only as adjunctive therapy. DMARDs offer symptomatic relief, have been shown to modify disease progression, and are currently the first-line therapy in early RA, being initiated within 3 months of disease onset. Examples of currently used DMARDs include MTX, leflunomide, sulfasalazine, and hydroxychloroquine, although MTX is by far the most common and best tolerated.

13

RHEUMATOID ARTHRITIS BIOLOGICS
Biologics (Table 8-1) significantly inhibit joint damage and are often used in combination with DMARDs to offer the most efficient suppression of disease. They include the __________-α inhibitors, __________-cell depletion, IL-6 and IL-1 inhibitors, and CTLA-4Ig. Adverse events, though less common, may be life threatening, and long-term effects are still unclear.
Arthroscopic __________ can be performed to reduce joint destruction and relieve symptoms not alleviated by conservative management.

RHEUMATOID ARTHRITIS BIOLOGICS
Biologics (Table 8-1) significantly inhibit joint damage and are often used in combination with DMARDs to offer the most efficient suppression of disease. They include the TNF-α inhibitors, B-cell depletion, IL-6 and IL-1 inhibitors, and CTLA-4Ig. Adverse events, though less common, may be life threatening, and long-term effects are still unclear.
Arthroscopic synovectomy can be performed to reduce joint destruction and relieve symptoms not alleviated by conservative management.

14

Juvenile Idiopathic Arthritis
JIA is a common childhood chronic illness, affecting some 70,000 to 100,000 persons younger than 16 years of age in the United States. There are seven subtypes: __________, polyarthritis RF __________, polyarthritis RF __________, __________ (persistent and extended), __________-related arthritis, __________, and undifferentiated. Girls are more frequently affected than boys, although this may vary with JIA subtype. Diagnosis requires onset prior to age 16 years, persistent arthritis in one or more joints for 6 or more weeks, and exclusion of other childhood arthritides. RF-positive subtype I is relatively less frequent, occurring in up to 10% of the JIA population. Oligoarticular JIA is characteristically seen in young girls (ages 1 to 5 years), is ANA positive, and is notable for its often asymptomatic uveitis (30% to 50%), which can lead to blindness. Other subtypes may also be complicated by ocular involvement. There is significant lifelong functional limitations in >30% of JIA patients after ≥10 years of follow-up. Many children do not reach the expected adult height. Ocular outcomes have improved, although they still represent a significant cause of blindness. Mortality rates are 3 to 14 times greater than expected. Unlike previously thought, many patients with JIA will continue to have active inflammatory arthritis in adulthood.

Juvenile Idiopathic Arthritis
JIA is a common childhood chronic illness, affecting some 70,000 to 100,000 persons younger than 16 years of age in the United States. There are seven subtypes: systemic, polyarthritis RF positive, polyarthritis RF negative, oligoarthritis (persistent and extended), enthesitis-related arthritis, psoriatic, and undifferentiated. Girls are more frequently affected than boys, although this may vary with JIA subtype. Diagnosis requires onset prior to age 16 years, persistent arthritis in one or more joints for 6 or more weeks, and exclusion of other childhood arthritides. RF-positive subtype I is relatively less frequent, occurring in up to 10% of the JIA population. Oligoarticular JIA is characteristically seen in young girls (ages 1 to 5 years), is ANA positive, and is notable for its often asymptomatic uveitis (30% to 50%), which can lead to blindness. Other subtypes may also be complicated by ocular involvement. There is significant lifelong functional limitations in >30% of JIA patients after ≥10 years of follow-up. Many children do not reach the expected adult height. Ocular outcomes have improved, although they still represent a significant cause of blindness. Mortality rates are 3 to 14 times greater than expected. Unlike previously thought, many patients with JIA will continue to have active inflammatory arthritis in adulthood.

15

Juvenile Idiopathic Arthritis Treatment: Similar to adults, treatment of JIA involves DMARD and biologic therapy with NSAIDs and systemic steroids as bridge therapy for symptomatic control. IA steroids (i.e., for acutely inflamed joints) can be used for pain control. __________ is used for JIA that is complicated by the macrophage activation syndrome and __________ for the systemic subtype, which tends to be less responsive to MTX and TNF inhibition. Prone lying and splints may prevent/correct contractures. Heat for nonacutely inflamed joints may help reduce stiffness. Physical therapy for flexibility and muscle strengthening is fundamental. Swimming, cycling, and isometric exercises are relatively less stressful to the joints.

Juvenile Idiopathic Arthritis Treatment: Similar to adults, treatment of JIA involves DMARD and biologic therapy with NSAIDs and systemic steroids as bridge therapy for symptomatic control. IA steroids (i.e., for acutely inflamed joints) can be used for pain control. Cyclosporine is used for JIA that is complicated by the macrophage activation syndrome and anakinra (Anakinra is an interleukin-1 (IL-1) receptor antagonist) for the systemic subtype, which tends to be less responsive to MTX and TNF inhibition. Prone lying and splints may prevent/correct contractures. Heat for nonacutely inflamed joints may help reduce stiffness. Physical therapy for flexibility and muscle strengthening is fundamental. Swimming, cycling, and isometric exercises are relatively less stressful to the joints.

16

ANKYLOSING SPONDYLITIS
AS is one of the classic seronegative __________. Risk factors include HLA-__________ and __________ gender (male to female incidence is __________: __________). Onset is typically in late adolescence or early adulthood. Initial symptoms include pain and stiffness in the buttock or lumbar area, which are worse with inactivity and improve with exercise or hot showers. B/l, symmetric __________ is a characteristic early X-ray finding. Inflammation of the spine can lead to __________ formation and then ultimately to a kyphotic bony ankylosis (“bamboo spine”). Progression of spinal inflexibility can be followed by __________ test. Although the course of AS is variable, the majority of patients have mild disease and normal longevity. Extra-articular manifestations include peripheral large joint arthritis, uveitis, cardiac conduction abnormalities, aortic regurgitation, and pulmonary fibrosis of the upper lobes. Uveitis typically is painful, monoarticular, and acute. It is associated with redness and photophobia and may progress to blindness.

ANKYLOSING SPONDYLITIS
AS is one of the classic seronegative spondyloarthropathies. Risk factors include HLA-B27 and male gender (male to female incidence is 2:1). Onset is typically in late adolescence or early adulthood. Initial symptoms include pain and stiffness in the buttock or lumbar area, which are worse with inactivity and improve with exercise or hot showers. B/l, symmetric sacroiliitis is a characteristic early X-ray finding. Inflammation of the spine can lead to syndesmophyte formation and then ultimately to a kyphotic bony ankylosis (“bamboo spine”). Progression of spinal inflexibility can be followed by Schober's test. Although the course of AS is variable, the majority of patients have mild disease and normal longevity. Extra-articular manifestations include peripheral large joint arthritis, uveitis, cardiac conduction abnormalities, aortic regurgitation, and pulmonary fibrosis of the upper lobes. Uveitis typically is painful, monoarticular, and acute. It is associated with redness and photophobia and may progress to blindness.

17

ANKYLOSING SPONDYLITIS Treatment includes spinal __________ exercises (e.g., swimming and push-ups), expansive chest breathing, pectoral and hip flexor stretching, and prone lying. A hard mattress, preferably w/o pillows behind the head, should be recommended. NSAIDs (e.g., naproxen and indomethacin) may reduce pain and symptoms of spinal stiffness. __________ is useful in cases of significant peripheral arthritis. TNF-α inhibitors should be used for patients with axial manifestations. Often hip replacement surgery is required.

ANKYLOSING SPONDYLITIS Treatment includes spinal extension exercises (e.g., swimming and push-ups), expansive chest breathing, pectoral and hip flexor stretching, and prone lying. A hard mattress, preferably w/o pillows behind the head, should be recommended. NSAIDs (e.g., naproxen and indomethacin) may reduce pain and symptoms of spinal stiffness. Sulfasalazine is useful in cases of significant peripheral arthritis. TNF-α inhibitors should be used for patients with axial manifestations. Often hip replacement surgery is required.

18

FIBROMYALGIA
FM is an incompletely understood clinical syndrome affecting women much more frequently than men. It is characterized by widespread, chronic pain and systemic symptoms (e.g., fatigue, sleep disturbance, and depression).
The ACR criteria include (1) pain and tenderness lasting for __________ months or longer (involving __________ sides, plus above and below the waist; in addition, axial skeletal pain must be present) and (2) pain in 11 or more of 18 predetermined tender points on examination (see below), elicited by applying approximately 4 kg/cm pressure (enough to blanch a fingernail). More recently, a __________ __________ diagnostic criterion has been introduced for use by primary care providers and underscores the chronic widespread nature of this pain syndrome.16 The SS score, with an emphasis on fatigue, nonrestorative sleep patterns, and cognitive abnormalities, is part of the diagnostic tool, but is envisioned to be useful in following the disease longitudinally (Fig. 8-1).

FIBROMYALGIA
FM is an incompletely understood clinical syndrome affecting women much more frequently than men. It is characterized by widespread, chronic pain and systemic symptoms (e.g., fatigue, sleep disturbance, and depression).
The ACR criteria include (1) pain and tenderness lasting for 3 months or longer (involving bilateral sides, plus above and below the waist; in addition, axial skeletal pain must be present) and (2) pain in 11 or more of 18 predetermined tender points on examination (see below), elicited by applying approximately 4 kg/cm pressure (enough to blanch a fingernail). More recently, a nontender point diagnostic criterion has been introduced for use by primary care providers and underscores the chronic widespread nature of this pain syndrome.16 The SS score, with an emphasis on fatigue, nonrestorative sleep patterns, and cognitive abnormalities, is part of the diagnostic tool, but is envisioned to be useful in following the disease longitudinally (Fig. 8-1).

19

FIBROMYALGIA Treatment should include __________ (e.g., FM typically has a nonprogressive course), low-impact aerobic activities, and analgesia. Recently, tai chi has been demonstrated to have a positive effect on pain and function in FM.17 Pharmaceutical options include low-dose __________ antidepressants at bedtime, SSRIs, NSAIDs, tramadol, pregabalin, duloxetine, and tender point injections. TENS, acupuncture, massage, and relaxation therapy are other options. The underlying depression should be addressed.

FIBROMYALGIA Treatment should include education (e.g., FM typically has a nonprogressive course), low-impact aerobic activities, and analgesia. Recently, tai chi has been demonstrated to have a positive effect on pain and function in FM.17 Pharmaceutical options include low-dose tricyclic antidepressants at bedtime, SSRIs, NSAIDs, tramadol, pregabalin, duloxetine, and tender point injections. TENS, acupuncture, massage, and relaxation therapy are other options. The underlying depression should be addressed.