MD Musculoskeletal disorders

Worsening with rest and improvement with activity is characteristic of seronegative spondyloarthropathies; degenerative disease usually improves with rest and is worse with activity. • Radiation down the buttock and below the knee, loss of reflexes, and a positive crossed straight-leg raise test result suggests nerve root irritation from a herniated disc.

NSAIDs are effective in early treatment. • Muscle “relaxants” (diazepam, cyclobenzaprine, carisoprodol, methocarbamol) Limited evidence that they provide short-term relief Best used if there is true muscle spasm that is painful Should be used with care due to potential for addiction • Opioids may be necessary to alleviate pain immediately. • Gabapentin and tricyclic antidepressants may be helpful in treating more chronic neuropathic pain.

A chronic systemic inflammatory disease of unknown cause with synovitis of multiple joints. • Pathological findings include chronic synovitis with pannus formation. • The pannus erodes cartilage, bone, ligaments, and tendons. • Females > males almost 3:1, peak onset in the fourth and fifth decades for women and sixth to eighth decade for men.

Radiographic changes are specific but insensitive, especially early in disease. • The earliest changes are swelling and juxta-articular demineralization in the hands or feet. • Joint space narrowing and erosions develop later in disease.

Drug-induced lupus (especially procainamide, hydralazine, and isoniazid) • Scleroderma • RA • Inflammatory myopathy, especially dermatomyositis • Rosacea • Vasculitis (eg, polyarteritis nodosa) • Endocarditis • Lyme disease

Low back pain may be categorized by pain on flexion versus pain on extension. • Nerve root impingement is suspected when pain is leg-dominant rather than back-dominant. • Alarming (“red flag”) symptoms or signs for serious spinal disease include unexplained weight loss, failure to improve with treatment, severe pain for >6 weeks, and night or rest pain. • The cauda equina syndrome often presents with bowel or bladder symptoms (or both) and is an emergency.

During an acute flare, a single serum uric acid determination is normal in up to 25% of cases, so it does not exclude gout. • However, serial measurements of serum uric acid detect hyperuricemia in 95% of patients.

• Muscular strain • Herniated disk • Lumbar spinal stenosis • Compression fracture • Degenerative joint disease • Infectious diseases (eg, osteomyelitis, epidural abscess, subacute bacterial endocarditis) • Neoplastic disease (vertebral metastases) • Seronegative spondyloarthropathies (eg, ankylosing spondylitis) • Leaking abdominal aortic aneurysm • Renal colic

Septic arthritis • Pseudogout (calcium pyrophosphate deposition disease) • Rheumatoid arthritis • Reactive arthritis • Osteoarthritis • Cellulitis • Chronic lead poisoning (saturnine gout) • Bursitis or bunion of the first MTP joint (podagra) • Sarcoidosis (podagra or tophi) • Polyarteritis nodosa or erythema nodosa (tophi)

Arthrocentesis is needed to diagnose superimposed septic arthritis, a common complication of RA.

Hip, knee, shoulder, and MCP joint replacements for long-standing, severe, erosive disease with destruction.

In overuse syndromes, rest and abstention from the causative physical activities for a period of days to weeks are essential, with subsequent gentle stretching to prevent recurrence. • Joint aspiration (arthrocentesis) is often both diagnostic and therapeutic.

Electromyography or nerve conduction studies may be useful in assessing patients with possible nerve root symptoms lasting >6 weeks, but are not usually necessary if the diagnosis of radiculopathy is clear.

Anti-CCP and RF are present in 70% to 80% with established RA. • RF has a sensitivity of only 50% in early disease. • Anti-CCP antibodies are the most specific blood test (specificity ~95%). • Approximately 20% of patients have antinuclear antibodies (ANA). • ESR and C-reactive protein are typically elevated in disease activity. • Anemia, leukopenia with splenomegaly (ie, Felty syndrome), and elevated platelet count are common.

Sudden onset of arthritis, frequently nocturnal Often the MTP joint of the great toe joint (“podagra”) is affected. Other common joints include the feet, ankles, and knees. • As the attack progresses: Pain becomes intense. Joints are red, tender, and swollen. Fever is common. • Tophi may be found in cartilage, external ears, hands, feet, olecranon, prepatellar bursae, tendons, and bone after several attacks of acute arthritis. • Asymptomatic periods of months or years commonly follow the initial attacks. • Years of recurrent severe attacks can evolve into a chronic, deforming disease that mimics rheumatoid arthritis.

Gout with tophi (mistaken for rheumatoid nodules) • Systemic lupus erythematosus • Infections such as parvovirus B19, Lyme disease, or rubella • Osteoarthritis or inflammatory osteoarthritis • Polymyalgia rheumatica • Hemochromatosis (MCP and wrist joints) • Rheumatic fever • Hepatitis B or C • Palindromic rheumatism • Hypertrophic pulmonary osteoarthropathy (paraneoplastic) • Systemic vasculitis, especially polyarteritis nodosa, mixed cryoglobulinemia or antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides

Early in the disease, radiographs show no changes. • Later, punched-out erosions with an overhanging rim of cortical bone (“rat bite”) develop.

Skin lesions often respond to the local administration of corticosteroids. • Minor joint symptoms can usually be alleviated by rest and nonsteroidal anti-inflammatory drugs. • Antimalarials (hydroxychloroquine) may be helpful in treating rashes or joint symptoms and appear to reduce the incidence of severe disease flares. • Corticosteroids are required for the control of certain serious complications, such as thrombotic thrombocytopenic purpura, hemolytic anemia, myocarditis, pericarditis, glomerulonephritis, alveolar hemorrhage, and CNS involvement. • Immunosuppressive agents such as cyclophosphamide, chlorambucil, and azathioprine are used in cases resistant to corticosteroids. Cyclophosphamide improves renal survival, but overall survival is no better than in those treated with prednisone. • Systemic corticosteroids are not usually given for minor arthritis, skin rash, leukopenia, or the anemia associated with chronic disease. • Belimumab is indicated for treatment of antibody-positive SLE patients with active disease who have not responded to standard therapies; its efficacy in severe disease activity is unknown and it appears less effective in blacks.

Cause is often multifactorial, although there are usually degenerative changes in the lumbar spine. • Alarming (“red flag”) symptoms for back pain caused by cancer include age >50 years; pain for >6 weeks; pain at night or rest; unexplained weight loss; failure to improve with treatment; history of cancer. • Alarming (“red flag”) symptoms for infection include fever; rest pain; recent infection (urinary tract infection, cellulitis, pneumonia); history of immunocompromise or injection drug use. • The cauda equina syndrome is suggested by urinary retention or incontinence; saddle anesthesia; decreased anal sphincter tone or fecal incontinence; bilateral lower extremity weakness; progressive neurologic deficits. • Risk factors for back pain due to vertebral fracture include age >70 years; use of corticosteroids; history of osteoporosis; recent significant trauma; presence of contusion. • Back pain may also be the presenting symptom in other serious problems, such as abdominal aortic aneurysm; peptic ulcer disease; kidney stones; pancreatitis. • Annual prevalence is 15% to 45%. • Most common cause of disability for patients under the age of 45 and second most common cause for primary care visits.

Joint symptoms Insidious onset, symmetric, polyarticular with tenderness, pain. Stiffness persisting for >30 minutes (and usually many hours) is prominent in the morning, recurs after inactivity or strenuous activity. PIP joints of the fingers, MCP joints, wrists, knees, ankles, and metatarsophalangeal joints most often involved. Synovial cysts and rupture of tendons and nerve entrapment (eg, median nerve in carpal tunnel of wrist) may occur. Neck can be affected, but the spine and sacroiliac joints are usually spared. In advanced disease, atlantoaxial (C1-C2) subluxation can lead to myelopathy. • Rheumatoid nodules over bony prominences, bursae, tendon sheaths, and other tissues are present in about 20% of patients. • Extra-articular manifestations correlate with the presence of RF in serum. • Ocular symptoms include scleritis, episcleritis, and dryness. • Other extra-articular manifestations include palmar erythema, vasculitis, interstitial lung disease, pericarditis, and pleural disease.

Complete blood count (CBC), uric acid level, and anti-CCP (anticyclic citrullinated protein) antibody testing may help identify infection, gout, or rheumatoid arthritis as the cause of an inflammatory arthritis. • Laboratory testing of aspirated joint fluid when indicated, can lead to a definitive diagnosis in most patients.

The Agency for Healthcare Research and Quality guidelines for obtaining lumbar radiographs include the above “red flag” symptoms and signs for cancer, vertebral fracture, or infection. • Diagnostic imaging, including radiographs, is not typically recommended in the first 6 weeks unless alarming “red flag” symptoms are present, which suggest infection, malignancy, or cauda equina syndrome. • If done, radiographs of the lumbar spine should include anteroposterior and lateral views. • Oblique views can be useful if the neural foramina or lesions need to be visualized. • MRI of the lumbosacral spine is the method of choice to evaluate symptoms not responding to conservative treatment or “red flags” for serious conditions.

Insidious onset with morning stiffness and symmetric joint pain • Polyarthritis with predilection for the small joints of the hands and feet • Radiographic juxta-articular osteoporosis; joint erosions and narrowing • RF and anti-CCP antibodies in 70% to 80% • Extra-articular manifestations, including subcutaneous nodules, interstitial lung disease, pleural effusion, pericarditis, splenomegaly with leukopenia, vasculitis

Physical examination includes palpating the relevant sites around the knee and special tests as noted above. • Arthrocentesis of joint fluid effusions should be done.

• Meniscal injury • Ligamentous tear or sprain • Osteoarthritis • Patellar dysfunction or misalignment • Fracture of the patella or tibia • Inflammatory arthritis • Septic arthritis • Ruptured popliteal (Baker) cyst • Prepatellar or anserine bursitis

Physical and occupational therapy, joint rest, heat and cold, exercise, splinting, and assistive devices.

Patients with SLE should avoid sun exposure and use sunscreen.

Common in Pacific Islanders (eg, Filipinos). • 90% of patients with primary gout are men. • Causes a recurring acute arthritis and later a chronic deforming arthritis. • Secondary gout from acquired hyperuricemia from Medications (diuretics, low-dose aspirin, cyclosporine, and niacin) Myeloproliferative disorders, multiple myeloma, hemoglobinopathies Chronic kidney disease Hypothyroidism, psoriasis, sarcoidosis, and lead poisoning • Alcohol ingestion increases urate production and decreases renal excretion of uric acid.

Systemic lupus erythematosus (SLE) is an inflammatory autoimmune disorder. • The clinical course is marked by spontaneous remissions and relapses. • Among SLE patients, females greatly outnumber males: 85% of patients are women. • SLE occurs in 1:1000 white women but in 1:250 black women. • Four features of drug-induced lupus separate it from SLE. The sex ratio in drug-induced lupus is nearly equal. Typically, it presents with fever, arthralgia, myalgia, and serositis but not nephritis and central nervous system (CNS) features. Hypocomplementemia and antibodies to double-stranded DNA are absent. It usually reverts toward normal when the offending drug is withdrawn.

Treatment of the acute attack focuses on reducing inflammation, not lowering serum uric acid. • NSAIDs are the treatment of choice; avoid aspirin. • Opioids for severe pain. • Oral colchicine for attacks with duration <36 hours. • Intravenous, oral, or intra-articular corticosteroids. • Bed rest to prevent early recurrence. • Interleukin-1 inhibitors (eg, anakinra) are under investigation for acute gouty arthritis.

Indications include cauda equina syndrome; cancer; infection; severe spinal deformity; ongoing morbidity with no response to >6 months of conservative treatment. • Surgery can improve pain but is unlikely to cure it.

• Fever, anorexia, malaise, and weight loss. • Skin lesions: photosensitivity, characteristic malar “butterfly” rash, alopecia. • Raynaud phenomenon (20% of patients) often antedates other symptoms. • Joint symptoms, with or without active synovitis, occur in >90% and are often the earliest manifestation. • Ocular: conjunctivitis, photophobia, blurring of vision, transient or permanent monocular blindness. • Pulmonary: pleurisy, pleural effusion, bronchopneumonia, pneumonitis, restrictive lung disease. • Cardiac: pericarditis, myocarditis, arrhythmias, verrucous endocarditis of Libman-Sacks. • Mesenteric vasculitis: aneurysms in medium-sized blood vessels, abdominal pain (particularly postprandial), ileus, peritonitis, and bowel perforation.“ • Neurologic: psychosis, cognitive impairment, seizures, peripheral and cranial neuropathies, transverse myelitis, strokes, severe depression (may be exacerbated by the administration of high-dose corticosteroids). • Glomerulonephritis: several forms may occur, including mesangial, focal and diffuse proliferative, and membranous.

Injuries may be caused by trauma, inflammation, infection, or degenerative changes. • Ligaments, menisci, synovium, or bursa may be affected. • Effusions can occur with intra-articular pathology (eg, osteoarthritis, injury or tear of a meniscus or cruciate ligament, patellar fracture or dislocation). • Overuse syndromes of the knee, such as anserine bursitis, iliotibial band syndrome, and popliteal or patellar tendinitis, occur often in runners who overtrain or who are not properly conditioned.

Patellofemoral pain—conservative symptomatic management with ice, anti-inflammatory medications, physical therapy (PT) targeted toward strengthening the posterolateral hip muscles which control rotation at the knee, brace or taping, surgery is a last resort—lateral release or patellar realignment surgery • Meniscus injury—in older patients with degenerative tears, treated conservatively with analgesics, PT; in younger patients with acute tears, arthroscopic meniscus debridement or repair • Posterior cruciate ligament (PCL) injury—unless there are associated neurovascular or other injuries (in up to one-third of cases), usually treated nonoperatively with knee brace locked in extension, crutches, gradual increase in range of motion • Collateral ligament injury MCL injury, tears rarely require surgery—grades 1–2 tears: PT, weight bearing as tolerated; grade 2 tear: hinged knee brace; grade 3 tear: long leg brace, weight-bearing only with brace locked in extension LCL injury, tears—almost always require surgery, reconstruction • Anterior cruciate ligament (ACL) injury—arthroscopic surgical reconstruction using patellar or hamstring tendon (autograft) or cadaver graft (allograft); in nonsurgical candidates, PT, ACL brace • Knee OA or RA—acetaminophen; topical NSAIDs can be effective in the treatment of osteoarthritis and avoid many of the traditional NSAID complications; knee replacement surgery in patients with significant disability

Examination of range of motion, effusions, meniscus, and ligaments • Evaluation of aspirated joint fluid if indicated

Sodium urate crystals in joint fluid or material aspirated from a tophus establishes the diagnosis. • The crystals are needle-like and negatively birefringent when examined by polarized light microscopy and may be extracellular or found within neutrophils.

Acute onset, usually monoarticular, recurring attacks of arthritis, often involving the first metatarsophalangeal (MTP) joint • Polyarticular involvement more common with long-standing disease • Hyperuricemia in most; identification of urate crystals in joint fluid or tophi is diagnostic • Dramatic therapeutic response to nonsteroidal anti-inflammatory drugs (NSAIDs)

Inquire about: location of knee symptoms; duration and rapidity of onset and the mechanism of injury or aggravating factors; stress or compression from sports, hobbies, or occupation; history of trauma or of orthopedic problems requiring surgery; symptoms of infection (fever, recent bacterial infections, risk factors for sexually transmitted or other bacterial infections) • Common symptoms Presence of grinding, clicking, or popping with bending may be indicative of osteoarthritis or the patellofemoral syndrome. “Locking” or “catching” when walking suggests an internal derangement such as meniscal injury or a loose body in the knee. Intra-articular swelling of the knee or an effusion indicates an internal derangement or a synovial pathology. Large swelling may cause a popliteal (Baker) cyst. Acute swelling within minutes to hours suggests a hemarthrosis, most likely due to an anterior cruciate ligament injury, fracture, or patellar dislocation, especially if trauma is involved. Lateral “snapping” with flexion and extension of the knee may indicate inflammation of the iliotibial band. Pain that is worsened with bending and walking downstairs suggests issues with the patellofemoral joint, such as chondromalacia of the patella or osteoarthritis. Pain that occurs when rising after prolonged sitting suggests a problem with tracking of the patella. • Swelling in the hollow or dimple around the patella and distention of the suprapatellar space may indicate knee joint effusion. • Specialized physical examination tests can help identify pathology: range of motion testing; Lachman test, anterior drawer test, and pivot shift test for ACL tear; valgus and varus stress tests for collateral ligament tears; posterior drawer test and “sag sign” for PCL tear; McMurray test, modified McMurray test, and Thessaly test for meniscal tear; apprehension sign for patellofemoral joint instability.

• Multiple system involvement • Rash over areas exposed to sunlight (photosensitivity) • Joint symptoms in 90% of patients • Anemia, leukopenia, thrombocytopenia • ANA with high titer antibodies to double-stranded DNA

In the standing position, observe the patient’s posture for spinal asymmetries including scoliosis, thoracic kyphosis, and lumbar hyperlordosis; assess the active range of motion of the lumbar spine; and perform the one-leg standing extension test to assess for pain (the patient stands on one leg while extending the spine); a positive test can be caused by pars interarticularis fractures (spondylolysis or spondylolisthesis) or facet joint arthritis. • In the sitting position, test motor strength, reflexes, and sensation, assess the major muscles in the lower extremities for weakness, compare the strength bilaterally to detect subtle muscle weakness, check sensory testing to light touch in specific dermatomes for corresponding nerve root function, and check the knee (femoral nerve L2-4), ankle (deep peroneal nerve L4-L5), and Babinski (sciatic nerve L5-S1) reflexes can be checked. • In the supine position, evaluate the hip for range of motion, focusing on internal rotation; perform the straight-leg raise test; it puts traction and compression forces on the lower lumbar nerve roots. • In the prone position, carefully palpate each level of the spine and sacroiliac joints for tenderness; and perform a rectal examination if the cauda equina syndrome is suspected.

Nonsteroidal anti-inflammatory drugs (NSAIDs) and cyclooxygenase (COX)-2 inhibitor provide some symptomatic relief but do not prevent erosions or alter disease progression. • Disease-modifying antirheumatic drugs (DMARDs) should be started as soon as the diagnosis is certain. • Methotrexate is the initial DMARD of choice. • Tumor necrosis factor inhibitors such as etanercept, infliximab, adalimumab, golimumab, and certolizumab pegol are DMARDs that work faster than methotrexate. • Hydroxychloroquine is useful for patients with mild disease. • Corticosteroids are effective orally in low doses, but side effects limit long-term use. • Intra-articular corticosteroids may be helpful for symptomatic relief if one or two joints are the chief source of difficulty but should not be given more than four times a year. • Leflunomide is a pyrimidine synthesis inhibitor nonbiologic DMARD. • Sulfasalazine is a second-line nonbiologic agent. • Other biologics for moderate-to-severe RA include abatacept, rituximab, and tocilizumab; tofacitinib is FDA approved for severe RA that is refractory to methotrexate and can be used either as monotherapy or in combination with methotrexate or other nonbiologic DMARD. • DMARDs generally have greater efficacy in combination (the most common current combination is that of methotrexate with one of the TNF inhibitors).

Nonpharmacologic treatments are key. Education alone improves patient satisfaction with recovery and recurrence. Strengthening and stabilization exercises effectively reduce pain and functional limitation compared with usual care. Physical therapy exercise programs can be tailored to the symptoms and pathology. Improvements in posture, core stability strengthening, physical conditioning, and modifications of activities to decrease physical strain are keys for ongoing management. • Heat and cold treatments may provide short-term symptom relief. • Spinal manipulation has not shown benefits and transcutaneous electrical nerve stimulation (TENS), back braces, physical agents, and acupuncture are unproven.

Reduce reversible causes, including a high-purine diet, obesity, frequent alcohol consumption, and trigger medications (diuretics, niacin, low-dose aspirin). • Colchicine can be used daily to prevent future attacks or prevent exacerbation when other treatments are initiated. • Probenecid and sulfinpyrazone are uricosuric drugs that can increase excretion of uric acid in those with intact renal function. • Allopurinol and febuxostat are xanthine oxidase inhibitors that can decrease uric acid production. • Pegloticase is a recombinant uricase agent. Given for refractory, chronic tophaceous gout, it converts uric acid to (readily excreted) allantoin.

Surgical excision of tophi rarely offers mechanical improvement in select cases.

Renal biopsy is useful in deciding whether treatment may be beneficial.

Plain weight-bearing radiographs may show degenerative changes or fractures. • MRI helps evaluate soft tissues, menisci, and ligaments. • CT and ultrasound are sometimes useful.

• Production of many different autoantibodies is seen. • ANA tests are sensitive but are not specific for diagnosis of SLE—ie, they are positive in low titer in up to 20% of healthy adults and also in many patients with nonlupus conditions such as RA, autoimmune thyroid disease, scleroderma, and Sjögren syndrome. • Antibodies to double-stranded DNA and to Sm are specific for SLE but not sensitive because they are present in only 60% and 30% of patients, respectively. • Depressed serum complement—a finding suggestive of disease activity—often returns toward normal in remission. • Three types of antiphospholipid antibodies occur. The first causes the biologic false-positive test results for syphilis. The second is lupus anticoagulant, a risk factor for venous and arterial thrombosis and miscarriage. The third is anticardiolipin antibody. • Abnormality of urinary sediment is almost always found in association with renal lesions. • Red blood cells (RBCs), with or without RBC casts, and mild proteinuria are frequent.