23 Arthritis and Rheumatologic Diseases - Bài viết - Bệnh Học
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23 Arthritis and Rheumatologic Diseases

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23 Arthritis and Rheumatologic Diseases
Hector Molina
Therapeutic Approaches to Rheumatic Disease
The etiology of most rheumatologic disorders is unknown. Therapeutic approaches in rheumatology are largely palliative. Such approaches involve either local or systemic administration of analgesic, anti-inflammatory, immunomodulatory, or immunosuppressive drugs. Because the same procedures and medications are used for most of the rheumatologic disorders, they are discussed as a group rather than separately under each disorder.
Joint Aspiration and Injection
Indications. Joint aspiration should be performed (a) when an effusion is present in a single joint and its etiology is unclear, (b) for symptomatic relief in a patient with a known arthritis diagnosis, and (c) to monitor the response to therapy in patients with infectious arthritis. Analysis of synovial fluid should include a cell count, microscopic examination for crystals, Gram stain, and culture. Intra-articular glucocorticoid therapy can be used to suppress inflammation when only one or a few peripheral joints are inflamed and infection has been excluded. The joint should be aspirated to remove as much fluid as possible before glucocorticoid injection. Glucocorticoid preparations include methylprednisolone acetate, triamcinolone acetonide, and triamcinolone hexacetonide. The dose used is arbitrary, but the following guidelines based on volume are useful: large joints (knee, ankle, shoulder), 1÷2 mL; medium joints (wrists, elbows), 0.5÷1.0 mL; and small joints of the hands and feet, 0.25÷0.5 mL. Lidocaine (or its equivalent), up to 1 mL of a 1% solution, can be mixed in a single syringe with the glucocorticoid to promote immediate relief but is not generally used in the digits.
Technique. The site of aspiration should be cleansed with povidone-iodine solution. Topical ethylchloride spray can be used as a local anesthetic. The site can also be infiltrated with local anesthetic in preparation for the procedure, particularly if there is little or no joint effusion or if there is notable joint space narrowing.
Knee. (See Fig. 23.1) The leg should be positioned by gently flexing the knee 10÷15 degrees. A rolled towel can be placed in the popliteal fossa to support the knee and allow the quadriceps to relax. The joint is then entered either medially or laterally, immediately beneath the undersurface of the patella.
Ankle. (See Fig. 23.2) Aspiration should be performed with the patient supine and the foot perpendicular to the leg. Medial aspiration is performed immediately medial to the extensor hallucis longus tendon, which can be identified by alternately flexing and extending the great toe. A lateral approach can also be used by introducing the needle just distal to the fibula.
Wrist. (See Fig. 23.3) Aspiration is performed on the dorsum of the wrist between the distal radius and carpus with the wrist joint flexed slightly. The point of entry for lateral aspiration is just distal to the end of the radius, between the extensor tendons of the thumb. Medial aspiration can also be performed between the distal ulna and the carpus.
Joints of the hands and feet. Small joints of the hands and feet are entered similarly by introducing the needle from the dorsal surface immediately beneath the extensor tendon from either the medial or the lateral side. Because these joints yield only very small amounts of fluid, flushing aspirate from the syringe with saline may increase the yield when analysis for crystals is attempted.
Contraindications
Infection overlying the site to be injected is an absolute contraindication.
Significant hemostatic defects and bacteremia are relative contraindications to joint aspiration and injection.
Complications
Postinjection synovitis may develop rarely as a result of phagocytosis of glucocorticoid ester crystals. Such reactions usually resolve within 48÷72 hours. More persistent symptoms suggest the possibility of iatrogenic infection, which occurs very rarely (in <0.1% of patients).
Localized skin depigmentation and atrophy may result after glucocorticoid injection. Accelerated deterioration of bone and cartilage also may occur when frequent injections are administered over an extended period. Therefore, any single joint should be injected no more frequently than every 3÷6 months.
Nonsteroidal Anti-inflammatory Drugs
Therapeutic effects. These drugs exert their effects by inhibiting the constitutive (COX-1) and inducible (COX-2) isoforms of cyclooxygenase, producing a mild to moderate anti-inflammatory and analgesic effect. Individual responses to these agents are variable: If one drug is not effective during a 2- to 3-week trial, another should be tried.
Side effects
Gastrointestinal (GI) toxicity manifests clinically as dyspepsia, nausea, vomiting, or GI bleeding. Nausea and dyspepsia often respond to the addition of a histamine-2 (H2)-blocking agent or proton pump inhibitor or to a change in nonsteroidal anti-inflammatory drugs (NSAIDs). Direct GI irritation can be minimized by administration after food, by the use of enteric-coated preparations, and by use of the lowest effective dose. However, all NSAIDs have a systemic effect on the GI mucosa, resulting in increased permeability to gastric acid. Most serious GI bleeds during NSAID use occur without prior GI symptoms. Risk factors for GI bleed include a history of duodenal-gastric ulceration, age, smoking, ethanol use, and concomitant use of corticosteroids. Misoprostol, a synthetic prostaglandin E analog, decreases the risk of NSAID-induced gastric or duodenal ulceration but may cause diarrhea and is an abortifacient. An alternative is high-dose famotidine, 40 mg PO bid, or omeprazole, 20 mg daily. Diarrhea due to NSAIDs is rare except for the fenamates (e.g., meclofenamic acid, mefenamic acid).
Acute renal failure is the most common form of renal toxicity, and nephrotic syndrome and acute interstitial nephritis may also occur. Risk factors for acute renal failure include pre-existing renal dysfunction, congestive heart failure (CHF), cirrhosis with ascites, and concomitant angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blockers. Periodic monitoring of renal function is recommended, particularly in elderly patients.
Platelet dysfunction can be caused by all NSAIDs, and particularly aspirin, which is a covalent inhibitor of cyclooxygenase. NSAIDs should be used cautiously or avoided in patients with a bleeding diathesis or those who are taking warfarin, and should be discontinued 5÷7 days before surgical procedures.
Hypersensitivity reactions are often seen in patients with a history of asthma, nasal polyps, or atopy. NSAIDs may cause a variety of type I hypersensitivity-like reactions, including urticaria, asthma, and anaphylactoid shock, presumably by increasing leukotriene synthesis. Patients with a hypersensitivity reaction to one NSAID should avoid all NSAIDs and selective COX-2 inhibitors.
Other side effects. Central nervous system (CNS) toxicity (headaches, dizziness, dysphoria, confusion, aseptic meningitis) is uncommon. Tinnitus and deafness can complicate NSAID use, particularly with high-dose salicylates. Blood dyscrasias including aplastic anemia have been observed as isolated case reports with ibuprofen, piroxicam, indomethacin, and phenylbutazone. Dermatologic reactions and elevations in transaminases have also been described. Acid-base imbalance is seen with high doses of salicylates. Nonacetylated salicylates have been reported to have less toxicity but also may be less effective. The use of NSAIDs, in general, may be associated with an increased risk for cardiovascular thrombotic events.
Selective COX-2 inhibitors
Therapeutic effects. These agents exhibit selective inhibition of COX-2, thereby inhibiting inflammation while preserving the homeostatic functions of constitutive COX-1÷derived prostaglandins. Their anti-inflammatory and analgesic efficacy are similar to that of traditional NSAIDs.
Side effects
GI symptoms and GI ulcerations are reduced with these agents in comparison to NSAIDs.
Platelet function is not impaired, making selective COX-2 inhibitors a good anti-inflammatory option for patients with thrombocytopenia, hemostatic defects, or chronic anticoagulation. In patients who are taking warfarin, however, the international normalized ratio (INR) should be monitored after the addition of a COX-2 inhibitor, as with any medication change. In addition, there has been controversy as to whether the inhibition of prostacyclin but not thromboxane by these agents may promote clotting slightly.
Fluid retention has been noted with high-dose rofecoxib therapy, and renal function should be monitored in patients at risk of NSAID-induced acute renal failure.
Patients with hypersensitivity reactions to NSAIDs should not use a COX-2 inhibitor, and individuals with a sulfonamide allergy should not use celecoxib.
An increased risk for myocardial infarction has been associated with the use of COX-2 inhibitors. The association is strongest for rofecoxib.
Glucocorticoids (Table 23-1)
Therapeutic effects. Glucocorticoids exert a pluripotent anti-inflammatory effect via the inhibition of inflammatory mediator gene transcription.
Preparations, dosages, and routes of administration. The goal of glucocorticoid therapy is to suppress disease activity with the minimum effective dosage. Prednisone (PO) and methylprednisolone (IV) are generally the preferred drugs because of cost and half-life considerations. IM absorption is variable and therefore is not advised. The dose, route, and frequency of administration are determined by the type of disease and the severity of the disease manifestations. The following are relative anti-inflammatory potencies of common glucocorticoid preparations: cortisone, 0.8; hydrocortisone, 1; prednisone, 4; methylprednisolone, 5; dexamethasone, 25.
Side effects. Adverse effects are related to dosage and duration of administration and, except for cataracts and osteopenia, can be minimized by alternate-day administration once the disease is controlled (twice the daily dose given every other day).
Adrenal suppression. Glucocorticoids suppress the hypothalamic-pituitary-adrenal axis. Patients who have received more than 10 mg prednisone (or the equivalent) daily for several weeks may have some degree of axis suppression for up to 1 year after cessation of therapy. Adrenal suppression is minimized by dosing in the morning and using a single daily low dose of a short-acting preparation, such as prednisone, for a short period. In patients who are receiving chronic glucocorticoid therapy, hypoadrenalism (anorexia, weight loss, lethargy, fever, and postural hypotension) may occur at times of severe stress (e.g., infection, major surgery) and should be treated with stress doses of glucocorticoids. Mineralocorticoid activity, however, is preserved. These patients should wear a medical-alert bracelet or carry identification.
TABLE 23-1 Corticosteroids and Immunomodulatory and Immunosuppressive Drugs
Generic name
Tablet size (mg)
Starting dose (mg)
Dose interval
Maximum daily or interval dose (mg)
Prednisone
1, 2.5, 5, 10, 20, 50
5÷20 (low), 1÷2 mg/kg (high)
Daily
—
Methylprednisolone (IV)
—
500
bid for 3÷5 d
—
Methotrexate
2.5
7.5
Weekly
25
Sulfasalazine
500
500
bid
3,000
Hydroxychloroquine
200
200
bid
400
Leflunomide
10, 20
20
Daily
20a
Azathioprine
50 (scored)
1.5 mg/kg
Daily
2.5÷3.0 mg/kgb
Cyclophosphamide
25, 50
1.0÷1.5 mg/kg
Daily
2.5÷3.0 mg/kgb
Cyclophosphamide (IV)
—
0.5÷1.0 g/m2
Monthly
—b,c
Cyclosporine
25, 50, 100
2÷3 mg/kg
Daily
5 mg/kg
aTreatment can be begun with a loading dose of 100 mg/d for 3 days.
bTitrate peripheral white blood cell count to 3,500÷4,500 cells/mcL (with neutrophils >1,000).
cThe addition of 2-mercaptoethanesulfonate (mesna) is recommended.
 Immunosuppression. Glucocorticoid therapy reduces resistance to infections. Bacterial infections in particular are related to the dosage of glucocorticoids and are a major cause of morbidity and mortality. Thus, minor infections may become systemic, quiescent infections may be activated, and organisms that usually are nonpathogenic may cause disease. Local and systemic signs of infection may be partially masked, although fever associated with infection generally is not suppressed completely by glucocorticoids. When possible, a skin test for tuberculosis should be placed before glucocorticoid therapy is instituted, and, if it is positive, appropriate prophylaxis is indicated (see Chapter 13, Treatment of Infectious Diseases).
Endocrine abnormalities. Possible endocrine abnormalities include a cushingoid habitus and hirsutism. Hyperglycemia may be induced or aggravated by glucocorticoids but usually is not a contraindication to therapy. Insulin therapy may be required, although ketoacidosis is rare. Fluid and electrolyte abnormalities include hypokalemia and sodium retention, which may induce or aggravate hypertension.
Musculoskeletal problems
Osteopenia with vertebral compression fractures is common among patients who are receiving long-term glucocorticoid therapy. Supplemental calcium, 1.0÷1.5 g/d PO, should be given along with vitamin D, 400÷800 units daily PO, as soon as steroid therapy is begun. A bisphosphonate may be indicated in postmenopausal women or in men or premenopausal women who are at high risk for osteopenia, and calcitonin can be considered for those who cannot tolerate a bisphosphonate. Determination of baseline bone density is appropriate in these patients. A judicious exercise program may be beneficial in stimulating bone formation.
Steroid myopathy generally involves the hip and shoulder girdle musculature. Muscles are weak but not tender and, in contrast to inflammatory myositis, serum creatine kinase, aldolase, and electromyography are normal. The myopathy usually resolves slowly with a reduction in glucocorticoid dosage and an aggressive exercise program.
Ischemic bone necrosis (aseptic necrosis, avascular necrosis) caused by glucocorticoid use often is multifocal, most commonly affecting the femoral head, humeral head, and tibial plateau. Early changes can be demonstrated by bone scan or magnetic resonance imaging (MRI). Early surgical intervention with core decompression remains controversial.
Other adverse effects. Changes in mental status ranging from mild nervousness, euphoria, and insomnia to severe depression or psychosis may occur. Ocular effects include increased intraocular pressure (sometimes precipitating glaucoma) and the formation of posterior subcapsular cataracts. Hyperlipidemia, menstrual irregularities, increased perspiration with night sweats, and pseudotumor cerebri also may occur.
Immunomodulatory and immunosuppressive drugs
These agents can be used to treat rheumatologic disorders (Table 23-1). This group of drugs includes a number of pharmacologically diverse agents that exert anti-inflammatory or immunosuppressive effects. Often, such agents are referred to as disease-modifying antirheumatic drugs. They are characterized by a delayed onset of action and the potential for serious toxicity. Consequently, they should be prescribed with the guidance of a rheumatologist or other physician who is experienced in their use and given only to well-informed, cooperative patients who are willing to comply with meticulous follow-up.
Methotrexate, a purine inhibitor and folic acid antagonist, is used to treat synovitis and myositis and may improve the leukopenia of Felty syndrome.
Dosage and administration. Typically, methotrexate is administered as a single PO dose once a week starting with 7.5 mg. Clinical response is usually noted in 4÷8 weeks. If no response is attained after 6÷8 weeks of therapy, the dosage can be increased by 2.5- to 5.0-mg increments every 2÷4 weeks to a maximum of 25 mg/wk or until improvement is observed. Dosages above 20 mg/wk are generally given by SC injection to promote absorption. Methotrexate in a dosage of 7.5÷17.5 mg/wk is
also used in a treatment regimen for rheumatoid arthritis (RA) in combination with sulfasalazine, 500 mg bid, and hydroxychloroquine, 200 mg bid.
Contraindications and side effects. Methotrexate is teratogenic and should not be used during pregnancy. It should also be avoided in patients with significant hepatic or renal impairment. Folic acid supplementation at a dosage of 1÷2 mg daily may reduce methotrexate toxicity without impeding its efficacy. Concomitant use of trimethoprim/sulfamethoxazole should be avoided.
Minor side effects include GI intolerance, stomatitis, rash, headache, and alopecia.
Bone marrow suppression may occur, particularly at higher doses. Blood and platelet counts should be obtained before initiation, monthly during the first 3÷4 months, and every 6÷8 weeks thereafter. Macrocytosis may herald serious hematologic toxicity and is an indication for folate supplementation, dose reduction, or both.
Cirrhosis may occur rarely with long-term use. Aspartate transaminase (AST), alanine transaminase (ALT), and serum albumin should be measured every 4÷8 weeks. Liver biopsy should be performed if the AST is elevated in five of nine determinations or if the serum albumin level falls below the normal range. Alcohol consumption increases the risk of methotrexate hepatotoxicity.
Hypersensitivity pneumonitis may occur but usually is reversible. Patients with pre-existing pulmonary parenchymal disease may be at increased risk.
Rheumatoid nodules may develop or worsen, paradoxically, in some patients on methotrexate.
Sulfasalazine is useful for treating synovitis in the setting of RA and the seronegative spondyloarthropathies.
Dosage. The initial dosage is 500 mg PO daily, with increases in 500-mg increments weekly until a total daily dose of 2,000÷3,000 mg (given in evenly divided doses) is reached. Clinical response usually occurs in 6÷10 weeks.
Contraindications and side effects. Sulfasalazine should not be used in patients with glucose-6-phosphate dehydrogenase deficiency or sulfa allergy. Nausea is the principal adverse effect and can be minimized by the use of the enteric-coated preparation of the drug. Hematologic toxicity including a reduction in any cell line and aplastic anemia rarely occurs. However, periodic monitoring of blood and platelet counts is warranted.
Hydroxychloroquine is an antimalarial agent that is used to treat dermatitis, alopecia, and synovitis in systemic lupus erythematosus (SLE) and mild synovitis in RA.
Dosage. Hydroxychloroquine typically is given at a dosage of 4÷6 mg/kg PO daily (200÷400 mg) after meals to minimize dyspepsia and nausea.
Contraindications and side effects. Hydroxychloroquine should not be used in patients with porphyria, glucose-6-phosphate dehydrogenase deficiency, or significant hepatic or renal impairment. It is probably safe during pregnancy. The most common side effects are allergic skin eruptions and nausea. Serious ocular toxicity occurs but is rare with currently recommended dosages. Ophthalmologic evaluation should be performed every 12÷18 months.
Leflunomide is a pyrimidine inhibitor that has been approved for the treatment of RA.
Dosage and administration. Treatment is begun with 10 or 20 mg PO daily. A loading dose of 100 mg for 3 days can be used. Clinical response is generally seen within 4÷8 weeks.
Contraindications and side effects. Leflunomide is teratogenic and has a very long half-life. Women who plan to become pregnant must discontinue the drug and complete a course of elimination therapy with cholestyramine, 8 g PO tid for 11 days. Plasma levels should then be verified to be <0.02 mg/L on two separate tests at least 14 days apart before pregnancy is considered. Leflunomide is contraindicated in patients with significant hepatic dysfunction or in those who are receiving rifampin. GI side effects are the most common. Diarrhea occurs in up to 20% of patients and may require discontinuation of the drug. Dosage reduction to 10 mg/d may provide relief while maintaining efficacy, and loperamide can be used for symptomatic relief. Elevations in serum transaminase levels may occur, and transaminase levels
should be measured at baseline and then monitored monthly. The dosage should be reduced for confirmed twofold elevations, and greater elevations should be treated with cholestyramine and discontinuation of leflunomide. Rash and alopecia may occur during therapy
Azathioprine is an antimetabolite that is used to treat refractory synovitis or myositis. It can also be used as a steroid-sparing agent.
Dosage. Therapy is initiated at 1.5 mg/kg/d PO, given as a single dose or in two divided doses. The dosage can be increased at 8- to 12-week intervals to a maximum of 2.5÷3.0 mg/kg/d as long as the white blood cell (WBC) count remains at or above 3,500÷4,500 cells/microliters with more than 1,000 neutrophils. The dosage of azathioprine should be reduced by 60%÷75% if it is given concomitantly with allopurinol, which blocks its metabolic degradation.
Side effects. Adverse effects of azathioprine include an increased incidence of infection, nausea, rare hepatotoxicity, and potential long-term oncogenicity.
Mycophenolate mofetil is an inhibitor of inosine monophosphate dehydrogenase used to treat lupus nephritis and, occasionally, as a steroid-sparing agent.
Dosage. Treatment is initiated at 1 g PO daily and can be increased to 2 g/d if the WBC remains at or above 3,500÷4,500 cells/microliters.
Side effects. The most common adverse effects with mycophenolate mofetil are nausea, diarrhea, and vomiting. Leukopenia and an increased frequency of opportunistic infections have also been reported.
Cyclophosphamide, an alkylating agent, is used to treat life-threatening manifestations of SLE and vasculitis.
Dosage and administration. Cyclophosphamide can be administered either daily (low-dose PO therapy) or intermittently (high-dose IV bolus therapy). The latter route is probably less toxic but also less immunosuppressive. Oral therapy is initiated at a daily morning dose of 1.0÷1.5 mg/kg and can be increased to a maximum of 2.5÷3.0 mg/kg/d to obtain a WBC count of 3,500÷4,500 cells/microliters, with more than 1,000 neutrophils. Peripheral WBC counts should be checked 10÷14 days after each dosage change and monthly when on a stable dose. IV therapy is initiated at a dosage of 0.5÷1.0 g/m2 every 1÷3 months. The goal of therapy is to achieve a nadir WBC count of 3,500÷4,500 cells/microliters, with more than 1,000 neutrophils, 10÷14 days after infusion.
Side effects. Adverse effects include an increased incidence of infection, hemorrhagic cystitis, GI toxicity (nausea, vomiting), gonadal suppression and sterility, alopecia, pulmonary interstitial fibrosis, and oncogenicity (particularly bladder carcinoma). Patients should be encouraged to take the medication in the morning with a lot of fluid, to void frequently, and to void before going to bed to minimize the risk of hemorrhagic cystitis. With IV therapy, sodium 2-mercaptoethanesulfonate (mesna) and large volumes of fluid can be given concomitantly to minimize the risk of hemorrhagic cystitis. Mesna can be administered concomitantly with the cyclophosphamide infusion and repeated 3 and 6 hours later. Each mesna dose should be 20% of the total cyclophosphamide dose. Antiemetics may be necessary with high-dose IV therapy. The use of trimethoprim/sulfamethoxazole three times a week for Pneumocystis carinii prophylaxis should be considered
Cyclosporine is occasionally used to treat refractory synovitis. Therapy is initiated at a dose of 2÷3 mg/kg/d PO. The dose can be increased to as high as 5 mg/kg/d, but renal toxicity is the usual limiting factor. The dosage should be reduced if the serum creatinine level increases more than 30% or if hypertension develops. Other toxicities include hirsutism, anemia, liver dysfunction, and oncogenicity.
Anticytokine therapies
New treatments directed at specific cytokines have been developed.
Tumor necrosis factor (TNF) inhibitors have been approved for treatment of RA and seronegative spondyloarthropathies, and have also been useful in some forms of vasculitis. In general, these agents are used in patients with moderate to severe RA who have
failed a trial of one or more disease-modifying antirheumatic drugs as listed above. Three preparations are currently available, with similar efficacy and toxicity profiles.
Etanercept is a fusion protein that consists of the ligand-binding portion of the human TNF receptor linked to the Fc portion of human immunoglobulin (Ig) G. It binds to TNF, blocking its interaction with cell surface receptors, thus inhibiting the inflammatory and immunoregulatory properties of TNF. This preparation is given in a dosage of 25 mg SC twice a week or 50 mg SC weekly.
Infliximab is a chimeric monoclonal antibody that binds specifically to human TNF-α, blocking its proinflammatory and immunomodulatory effects. It is given by IV infusion in conjunction with methotrexate to reduce production of neutralizing antibodies against infliximab. The recommended treatment regimen includes infliximab infusions of 3 mg/kg at initiation, at 2 and 6 weeks, and every 8 weeks thereafter, along with methotrexate at a dose of at least 7.5 mg/wk.
Adalimumab is a recombinant human IgG-1 monoclonal antibody that is specific to human TNF-α. It can be given in a dosage of 40 mg SC every other week. Some patients form antiadalimumab antibodies, and their regimen may include weekly injections of adalimumab or the addition of low-dose methotrexate. The effect of these agents on RA synovitis can be dramatic, with responsive patients reporting the onset of symptomatic benefits within 1÷2 weeks. In addition to their symptomatic benefits, these agents appear to retard joint damage significantly.
Contraindications and side effects
Serious infections and sepsis, including fatalities, have been reported during the use of TNF-blocking agents. These drugs are contraindicated in patients with acute or chronic infections, and if serious infection or sepsis occurs, the drug should be stopped. Those with a history of recurrent infections and those with underlying conditions that may predispose to infection should be treated with caution and counseled to be vigilant for signs and symptoms of infection. Upper respiratory and sinus infections are most common. Tuberculosis has also been noted, and a tuberculin skin test and chest radiograph should be obtained before beginning therapy. Patients who are undergoing elective surgical procedures can omit the last dose of the drug that is scheduled to be given before surgery, as well as the next dose scheduled to follow the surgery. These agents are also contraindicated in patients with congestive heart failure.
Local injection site reactions are common with etanercept and adalimumab, particularly during the first month of therapy. These reactions are generally self-limited and do not require discontinuation of therapy. Serious systemic allergic reactions are rare but may occur with infliximab infusions.
Other adverse effects may include induction of antinuclear antibodies and, rarely, a lupuslike illness. A demyelinating disorder has been described, as well as exacerbations of pre-existing multiple sclerosis. It is unclear whether the frequency of occurrence of lymphoma may be increased in patients who receive these agents.
Inhibitors of interleukin-1α (IL-1). Currently, only one inhibitor of interleukin is available for patients with rheumatic diseases, but several more are in development.
Anakinra is a recombinant form of the naturally occurring IL-1÷receptor antagonist that is approved for use in RA. It blocks binding of IL-1 to its receptor, thus inhibiting the proinflammatory and immunomodulatory actions of IL-1.
This agent is given in a dosage of 100 mg SC daily. Like the TNF blockers, it should not be prescribed to patients with ongoing or recurrent infections.
Adverse effects include an increased frequency of bacterial infections and injection site reactions.
Anakinra should not be used in conjunction with a TNF blocker because of enhanced risk of serious infection and neutropenia.
Plasmapheresis
Until concomitant therapy with glucocorticoids or immunosuppressives has taken effect, plasmapheresis has been used on an investigational basis in life-threatening situations
to control various rheumatic diseases. It is an impractical long-term therapy, and its short-term use remains controversial. A new approach, pheresis across a column bound with staphylococcal protein A, the Prosorba column, has been approved for treatment of RA.
Approach to the Patient with a Single Painful Joint
Diagnosis
Physical Examination
The first step for diagnosis for a patient with a single painful joint is to identify the structure involved. Pain that arises from periarticular (e.g., tendon, bursa), muscular, and neurologic structures may be perceived as joint pain.
Differential Diagnosis
If the pain arises in the joint itself and a single joint is involved, the major disorders in the differential diagnosis are trauma, infection, and crystalline arthritis.
Imaging
Radiographs of the joint may be useful in documenting trauma or pre-existing joint disease. The presence of chondrocalcinosis on the radiograph suggests pseudogout but is not diagnostic (see Crystal-Induced Synovitis). Radiographs are usually normal in acute infectious or crystalline arthritis.
Diagnostic Procedures
Synovial fluid should be aspirated in all patients with a monarticular arthritis who do not have a pre-existing diagnosis that is consistent with the clinical picture. Polyarticular disorders such as RA or lupus (SLE) occasionally present initially as monarthritis, but when a single joint is inflamed out of proportion to other joints in what is typically a polyarticular disorder, infection must be excluded. Synovial fluid cell counts above 5,000 nucleated cells/microliters suggest an inflammatory etiology. Counts above 50,000 cells/microliters may indicate infection, particularly if 75% or more of the cells are polymorphonuclear.
Treatment
Management is based on the results of radiographs and synovial fluid analysis. Trauma or internal derangement of the joint can be managed by immobilization of the joint and consultation with an orthopedic surgeon.
Infectious Arthritis and Bursitis
General Principles
Classification
Infectious arthritis is generally categorized into gonococcal and nongonococcal disease.
Etiology
Nongonococcal infectious arthritis in adults tends to occur in patients with previous joint damage or compromised host defenses. In contrast, gonococcal arthritis causes one-half of all septic arthritis in otherwise healthy, sexually active young adults.
Diagnosis
Clinical Presentation
The usual presentation is with fever and an acute monarticular arthritis, although multiple joints may be affected by hematogenous spread of pathogens.
Laboratory Studies
A joint fluid leukocyte count is useful diagnostically and as a baseline for serial studies to evaluate response to treatment. Cultures of blood and other possible extra-articular sites of infection also should be obtained.
Diagnostic Procedures
Joint fluid examination, including Gram stain of a centrifuged pellet, a joint fluid leukocyte count, and cultures are mandatory to make a diagnosis and to guide management.
Treatment
IV antimicrobials provide good serum and synovial fluid drug concentrations.
Oral or intra-articular antimicrobials are not appropriate as initial therapy.
An NSAID or a selective COX-2 inhibitor (see Therapeutic Approaches to Rheumatic Disease) is often useful to reduce pain and increase joint mobility but should not be used until response to antimicrobial therapy has been demonstrated by symptomatic and laboratory improvement.
Surgical drainage or arthroscopic lavage and drainage are indicated for (a) a septic hip; (b) joints in which either the anatomy, large amounts of tissue debris, or loculation of pus prevent adequate needle drainage (most commonly the shoulder); (c) septic arthritis with coexistent osteomyelitis; (d) joints that do not respond in 3÷5 days to appropriate therapy and repeated arthrocenteses; and (e) prosthetic joint infection.
General supportive measures include splinting of the joint, which may help to relieve pain. However, prolonged immobilization can result in joint stiffness.
Hospitalization is indicated to ensure drug compliance and careful monitoring of the clinical response.
Repeated arthrocenteses should be performed daily or as often as necessary to prevent reaccumulation of fluid. Arthrocentesis is indicated to (a) remove destructive inflammatory mediators, (b) reduce intra-articular pressure and promote antimicrobial penetration into the joint, and (c) monitor response to therapy by documenting sterility of synovial fluid cultures and steadily decreasing leukocyte counts.
Nongonococcal Septic Arthritis
General Considerations
Etiology
Nongonococcal septic arthritis is caused most often by Staphylococcus aureus (60%) and Streptococcus species. Gram-negative organisms are less common except with IV drug abuse, neutropenia, concomitant urinary tract infection, and postoperative patients.
Diagnosis
Diagnosis is made with a carefully performed Gram stain, which reveals the organism in approximately 50% of patients.
Treatment
Initial therapy is based on the clinical situation.
With a positive Gram stain, antibiotic coverage can be focused accordingly.
With a nondiagnostic Gram stain, antibiotics should be chosen to cover S. aureus, Streptococcus species, and Neisseria gonorrhoeae in otherwise healthy patients, whereas broad-spectrum antibiotics are appropriate in immunosuppressed patients.
IV antimicrobials usually are given for at least 2 weeks, followed by 1÷2 weeks of oral antimicrobials, with the course of therapy tailored to the patient's response.
Gonococcal Arthritis
General Principles
Epidemiology
Gonococcal arthritis is more common than nongonococcal septic arthritis.
Diagnosis
Clinical Presentation
The clinical spectrum of disease often includes migratory or additive polyarthralgias, followed by tenosynovitis or arthritis of the wrist, ankle, or knee and asymptomatic dermatitis on the extremities or trunk.
Laboratory Studies
In contrast to nongonococcal septic arthritis, Gram staining of synovial fluid and cultures of blood or synovial fluid often are negative.
Bacteriologic assessment of the throat, cervix, urethra, and rectum may aid in establishing the diagnosis.
Treatment
Initial treatment is with an IV antibiotic for the first 1÷3 days, generally ceftriaxone, 1 g IV daily, or ceftizoxime, 1 g IV q8h. Response to IV antibiotics is usually noted within the first 24÷36 hours of treatment. After clinical improvement is noted, therapy is continued with an oral antibiotic to complete 7÷10 days of treatment. Ciprofloxacin, 500 mg PO bid, or amoxicillin/clavulanate, 500÷850 mg PO bid, can be used. Treatment of coexisting Chlamydia infection should also be considered.
Nonbacterial Infectious Arthritis
Nonbacterial infectious arthritis is common with many viral infections, especially hepatitis B, rubella, mumps, infectious mononucleosis, parvovirus, enterovirus, and adenovirus.
It is generally self-limiting, lasting for <6 weeks, and responds well to a conservative regimen of rest and NSAIDs.
Arthralgias (often severe) or a reactive arthritis can also be a manifestation of HIV infection.
A variety of fungi and mycobacteria can cause septic arthritis and should be considered in patients with chronic monoarticular arthritis.
Septic Bursitis
Diagnosis
Usually involving the olecranon or prepatellar bursa, it can be differentiated from septic arthritis by localized, fluctuant superficial swelling and by relatively painless joint motion (particularly extension).
Most patients have a history of previous trauma to the area or an occupational predisposition (e.g., “housemaid's knee,” “writer's elbow”).
S. aureus is the most common pathogen of septic bursitis.
Treatment
Septic bursitis should be treated with aspiration, which can be repeated if fluid reaccumulates. Oral antibiotics and outpatient management are usually appropriate, and surgical drainage is rarely indicated.
Preventive measures (e.g., knee pads) should be used in patients with occupational predispositions to septic bursitis.
Lyme Disease
General Principles
Etiology
Lyme disease is caused by the tick-borne spirochete Borrelia burgdorferi.
Diagnosis
Typical manifestations begin with an erythematous annular rash (erythema migrans) and flulike symptoms.
Arthralgias, myalgias, meningitis, neuropathy, and cardiac conduction defects may follow in weeks to a few months. Months later, an intermittent or chronic arthritis in one or a few joints, characteristically including the knee, may develop in untreated patients.
The diagnosis is based mainly on the clinical picture and exposure in an endemic area.
Laboratory Studies
Unfortunately, serologic studies often give false-negative or false-positive results, and patients may remain seropositive for years following treatment.
Treatment
Antibiotic therapy is required.
NSAIDs are a useful adjunct for arthritis.
Risk Management
A vaccine against Lyme disease is safe and effective but was withdrawn from the market by the manufacturer due to limited demand.
Crystal-Induced Synovitis
General Principles
Definition
Deposition of microcrystals in joints and periarticular tissues results in gout, pseudogout, and apatite disease.
Epidemiology
Primary gouty arthritis. Men are much more commonly affected than women; most premenopausal women with gout have a family history of the disease.
Classification
The clinical phases of gout can be divided into (a) asymptomatic hyperuricemia, (b) acute gouty arthritis, and (c) chronic arthritis.
Asymptomatic hyperuricemia (uric acid levels >8 mg/dL in men and >7 mg/dL in women)
Etiology
Primary gouty arthritis is characterized by hyperuricemia that is usually due to underexcretion of uric acid (90% of cases) rather than to overproduction. Urate crystals may be deposited in the joints, SC tissues (tophi), and kidneys.
Secondary gout, like primary gout, can be caused by either defective renal excretion or overproduction of uric acid. Intrinsic renal disease, diuretic therapy, low-dose aspirin, nicotinic acid, cyclosporine, and ethanol all interfere with renal excretion of uric acid. Starvation, lactic acidosis, dehydration, pre-eclampsia, and diabetic ketoacidosis also can induce hyperuricemia.
Pseudogout results when calcium pyrophosphate dihydrate crystals deposited in bone and cartilage are released into synovial fluid and induce acute inflammation. Risk factors include older age, advanced osteoarthritis (OA), neuropathic joint, gout, hyperparathyroidism, hemochromatosis, diabetes mellitus, hypothyroidism, and hypomagnesemia.
Diagnosis
Clinical Presentation
Acute gouty arthritis presents as an excruciating attack of pain, usually in a single joint of the foot or ankle. Occasionally, a polyarticular onset can mimic RA.
Chronic gouty arthritis. With time, acute gouty attacks occur more frequently, asymptomatic periods are shorter, and chronic joint deformity may appear. Overproduction of uric acid occurs in myeloproliferative and lymphoproliferative disorders, hemolytic anemia, polycythemia, and cyanotic congenital heart disease.
Pseudogout may present as an acute monarthritis or oligoarthritis mimicking gout or as a chronic polyarthritis resembling RA or OA. Usually the knee or wrist is affected, although any synovial joint can be involved.
Apatite disease may present with periarthritis or tendonitis, particularly in patients with chronic renal failure. An episodic oligoarthritis also may occur.
History
Acute gouty arthritis attacks can be precipitated by surgery, dehydration, fasting, binge eating, or heavy ingestion of alcohol. Although the acute gouty attack will subside spontaneously over several days, prompt treatment can abort the attack within hours.
Laboratory Studies
A definitive diagnosis of gout or pseudogout is made by finding intracellular crystals in joint fluid examined with a compensated polarized light microscope. Urate crystals, which are diagnostic of gout, are needle shaped and strongly negatively birefringent. The calcium pyrophosphate dihydrate crystals seen in pseudogout are pleomorphic and weakly positively birefringent. Hydroxyapatite complexes, diagnostic of apatite disease, and basic calcium phosphate complexes can be identified only by electron microscopy
and mass spectroscopy. In most cases, the arthritides associated with these compounds are suspected clinically but never confirmed.
Acute gouty arthritis. The serum uric acid level is normal in 30% of patients with acute gout and, if elevated, should not be manipulated until an attack has resolved.
Apatite disease should be suspected when no crystals are present in the synovial fluid.
Imaging
Erosive arthritis may be seen.
Treatment
Asymptomatic hyperuricemia is not routinely treated because of expense, potential drug toxicity, and the low risk for adverse outcome from the hyperuricemia itself.
Management of secondary gout includes treatment of the underlying disorder and allopurinol therapy.
The treatment of apatite disease is similar to that for pseudogout.
Medications
Acute gout
NSAIDs are the treatment of choice due to ease of administration and low toxicity. Clinical response may require12÷24 hours, and initial doses should be high, followed by rapid tapering over 2÷8 days (see Therapeutic Approaches to Rheumatic Disease). One approach is to use indomethacin, 50 mg PO q6h for 2 days, followed by 50 mg PO q8h for 3 days and then 25 mg PO q8h for 2÷3 days. The long-acting NSAIDs generally are not recommended for acute gout. Selective COX-2 inhibitors appear to have similar efficacy.
Glucocorticoids are useful when NSAIDs are contraindicated. An intra-articular injection of glucocorticoids produces rapid dramatic relief. Alternatively, prednisone, 40÷60 mg PO daily, can be given until a response is obtained and then should be tapered rapidly.
Colchicine is most effective if given in the first 12÷24 hours of an acute attack and usually brings relief in 6÷12 hours. In view of the efficacy and tolerability of a short course of NSAIDs, colchicine is not commonly used to treat gout but is useful when NSAIDs or glucocorticoids are contraindicated or not tolerated.
Oral administration is often associated with severe GI toxicity. The dosage during an acute attack is 0.5÷0.6 mg (one tablet) q1÷2h for three dosages started at the first sign of the attack. Alternatively, colchicine 0.6 mg bid in addition to an NSAID can be used. The previous dosage regimen of 0.5÷0.6 mg (one tablet) q1÷2h or 1.0÷1.2 mg q2h until symptoms abate, GI toxicity develops, or the maximum dose of 6 mg in a 24-hour period is reached is not recommended as primary treatment for most cases due to toxicity.
IV colchicine is not recommended for general use and its administration in almost all circumstances is questionable.
Chronic gouty arthritis
Colchicine (0.5÷0.6 mg PO daily or bid) can be used prophylactically for acute attacks. The dosage needs to be adjusted in patients with renal insufficiency. Colchicine 0.6 mg every other day or every 3 days should be considered in patients with a creatinine clearance between 10 and 34 mL/min. Aspirin (uricoretentive), diuretics, large alcohol intake, and foods high in purines (sweetbreads, anchovies, sardines, liver, and kidney) should be avoided. The serum uric acid level should be lowered if arthritic attacks are frequent, renal damage is present, or serum or urine uric acid levels are elevated consistently. Maintenance colchicine, 0.5÷0.6 mg PO bid, should be given a few days before manipulation of the uric acid level to prevent precipitation of an acute attack. If no attacks occur after the uric acid has been maintained in the normal range for 6÷8 weeks, colchicine can be discontinued.
Allopurinol, a xanthine oxidase inhibitor, is effective therapy for hyperuricemia in most patients.
Dosage and administration. The initial dosage is usually 300 mg PO daily. Daily doses can be increased by 100 mg every 2÷4 weeks to achieve the minimum maintenance dosage that will keep the uric acid level within the normal range. In patients with impaired renal function, the daily dose should be reduced by 50 mg for each 20-mL/min decrease in the creatinine clearance. For patients with a creatinine clearance below 20 mL/min, the starting dosage is 100 mg every other or every third day. The daily dose should be decreased also in patients with hepatic impairment. The concomitant use of a uricosuric agent may hasten the mobilization of tophi. If an acute attack occurs during treatment with allopurinol, it should be continued at the same dosage while other agents are used to treat the attack.
Side effects. Hypersensitivity reactions from a minor skin rash to a diffuse exfoliative dermatitis associated with fever, eosinophilia, and a combination of renal and hepatic injury occur in up to 5% of patients. Patients who have mild renal insufficiency and are receiving diuretics are at greatest risk. Severe cases are potentially fatal and usually require glucocorticoid therapy. Allopurinol may potentiate the effect of oral anticoagulants and blocks metabolism of azathioprine and 6-mercaptopurine, necessitating a 60%÷75% reduction in dosage of these cytotoxic drugs.
Febuxostat, a new class of uric acid÷lowering drug, is a nonpurine selective inhibitor of the xanthine oxidase that is expected to be available soon in the United States.
Uricase catabolizes uric acid to the more soluble compound, allantoin. It is available in the United States for the treatment of tumor lysis syndrome.
Uricosuric drugs lower serum uric acid levels by blocking renal tubular reabsorption of uric acid. A 24-hour measurement of creatinine clearance and urine uric acid should be obtained before therapy is started, as these drugs are ineffective with glomerular filtration rates of <50 mL/min. They are also not recommended for patients who already have high levels of urine uric acid (800 mg/24 hours) because of the risk of urate stone formation. This risk can be minimized by maintaining a high fluid intake and by alkalinizing the urine. If these drugs are being used when an acute gouty attack begins, they should be continued while other drugs are used to treat the acute attack.
Probenecid
Initial dosage is 500 mg PO daily, which can be raised in 500-mg increments every week until serum uric acid levels normalize or urine uric acid levels exceed 800 mg/24 hours. The maximum dose is 3,000 mg/d. Most patients require a total of 1.0÷1.5 g/d in two to three divided doses.
Salicylates and probenecid are antagonistic and should not be used together.
Probenecid decreases renal excretion of penicillin, indomethacin, and sulfo- nylureas.
Side effects are minimal.
Sulfinpyrazone has uricosuric efficacy similar to that of probenecid; however, it also inhibits platelet function. The initial dosage of 50 mg PO bid can be increased in 100-mg increments weekly until serum uric acid levels normalize, to a maximum dose of 800 mg/d. Most patients require 300÷400 mg/d in three to four divided doses.
Pseudogout
As in gout, the therapy of choice for most patients is a brief high-dose course of an NSAID (see Therapeutic Approaches to Rheumatic Disease).
Oral corticosteroids can be used and colchicine also may relieve symptoms promptly, but toxicity limits its use. Dosage and administration are similar to the ones used in the treatment of gout.
Maintenance daily PO colchicine may diminish the number of recurrent attacks. Allopurinol or uricosuric agents have no role in treating pseudogout.
Aspiration of the inflammatory joint fluid often results in prompt improvement and intra-articular injection of glucocorticoids may hasten the response.
Rheumatoid Arthritis
General Principles
Definition
RA is a systemic disease of unknown etiology that is characterized by symmetric inflammatory polyarthritis, extra-articular manifestations (rheumatoid nodules, pulmonary fibrosis, serositis, vasculitis), and serum rheumatoid factor in up to 80% of patients.
Diagnosis
Clinical Presentation
The course of RA is variable but tends to be chronic and progressive.
Sjogren's syndrome, characterized by failure of exocrine glands, occurs in a subset of patients with RA, producing sicca symptoms (dry eyes and mouth), parotid gland enlargement, dental caries, and recurrent tracheobronchitis.
Felty's syndrome, the triad of RA, splenomegaly, and granulocytopenia, also occurs in a small subset of patients, and these patients are at risk for recurrent bacterial infections and nonhealing leg ulcers.
Approximately 70% of patients show irreversible joint damage on radiography within the first 3 years of disease. Work disability is common, and life span is shortened by between 3 and 12 years.
Reactive depression and sleep disorders are often encountered in patients with rheumatic diseases.
Treatment
Most patients can benefit from an early aggressive treatment program that combines medical, rehabilitative, and surgical services designed with three distinct goals: (a) early suppression of inflammation in the joints and other tissues, (b) maintenance of joint and muscle function and prevention of deformities, and (c) repair of joint damage to relieve pain or improve function.
Behavioral
Acute care of inflammatory arthritides involves joint protection and pain relief. Proper joint positioning and splints are important elements in joint protection. Heat is a useful analgesic.
Subacute disease therapy should include a gradual increase in passive and active joint movement.
Chronic care encompasses instruction in joint protection, work simplification, and performance of activities of daily living. Adaptive equipment, splints, orthotics, and mobility aids may be useful. Specific exercises designed to promote normal joint mechanics and to strengthen affected muscle groups are useful. Overall cardiac conditioning also improves functional status.
Sicca symptoms (dry eyes and mouth) can be treated symptomatically with artificial tears and saliva. Assiduous dental and ophthalmologic care is recommended, and drugs that suppress lacrimal÷salivary secretion further should be avoided.
Medications
NSAIDs or selective COX-2 inhibitors (see Therapeutic Approaches to Rheumatic Disease) are used as the initial therapy for RA and as an adjunct to immunomodulatory÷immunosuppressive therapy. A longer-acting NSAID may facilitate patient compliance.
Glucocorticoids are not curative and probably do not alter the natural history of RA; however, they are among the most potent anti-inflammatory drugs available (see Therapeutic Approaches to Rheumatic Disease). Unfortunately, once systemic glucocorticoid therapy has been initiated, few RA patients are able to discontinue it completely.
Indications for glucocorticoids include (a) symptomatic relief while waiting for a response to a slow-acting immunosuppressive or immunomodulatory agent, (b) persistent synovitis despite adequate trials of NSAIDs and immunosuppressive or immunomodulatory agents, and (c) severe constitutional symptoms (e.g., fever and weight loss) or extra-articular disease (vasculitis, episcleritis, or pleurisy).
Oral administration of prednisone 5÷20 mg daily usually is sufficient for the treatment of synovitis, whereas severe constitutional symptoms or extra-articular disease may require up to 1 mg/kg PO daily. Although alternate-day glucocorticoid therapy reduces the incidence of undesirable side effects, some patients do not tolerate the increase in symptoms that may occur on the off day.
Intra-articular administration may provide temporary symptomatic relief when only a few joints are inflamed (see Therapeutic Approaches to Rheumatic Disease). The beneficial effects of intra-articular steroids may persist for days to months and may delay or negate the need for systemic glucocorticoid therapy.
Immunomodulatory and immunosuppressive agents appear to alter the natural history of RA by retarding the progression of bony erosions and cartilage loss. Because RA may lead to substantial long-term disability (and is associated with increased mortality), the current trend is to initiate therapy with such agents early in the course of RA (see Therapeutic Approaches to Rheumatic Disease). Once a clinical response has been achieved, the chosen drug usually is continued indefinitely at the lowest effective dosage to prevent relapse.
Indications for the use of immunomodulatory or immunosuppressive agents include (a) active synovitis that does not respond to conservative management (e.g., NSAIDs); (b) rapidly progressive, erosive arthritis; and (c) dependence on steroids to control synovitis.
Selection of an immunomodulatory or immunosuppressive agent is tailored to the character of the patient's disease, taking into account the potential toxicity of these agents (see Therapeutic Approaches to Rheumatic Disease) (Table 23-1). Methotrexate typically is the initial choice for moderate to severe RA. Hydroxychloroquine or sulfasalazine can be used as the initial choice in very mild RA. If response to the initial agent is unsatisfactory after an adequate trial (or if limiting toxicity supervenes), an alternate agent, such as leflunomide, a TNF or IL-1 blocker, or azathioprine, can be used. Rituximab, a monoclonal antibody directed against the B-cell surface molecule CD20, causes depletion of B cells and has been shown to be effective in cases of severe rheumatoid arthritis not responding to conventional treatment. It is U.S. Food and Drug Administration (FDA) approved to be used routinely for RA. Abatacept is a fusion protein comprising the CTLA4 molecule and the Fc portion of IgG1. It blocks selective costimulation of T cells.
Combinations of immunomodulatory÷immunosuppressive agents can be used if the patient has a partial response to the initial agent.
Common combination therapies include methotrexate with either hydroxychloroquine, sulfasalazine, or both (see Therapeutic Approaches to Rheumatic Disease). For severe RA, methotrexate has been combined with leflunomide, azathioprine, or cyclosporin A. Such combinations may lead to synergistic or unexpected toxicities and should be used with appropriate caution.
Reactive depression and sleep disorders are often encountered in patients with rheumatic diseases. Judicious use of antidepressants and sedatives may improve the functional status of selected patients.
Sicca symptoms
Pilocarpine in a dosage of up to 5 mg PO qid may provide symptomatic relief.
Surgery
Corrective surgical procedures, including synovectomy, total joint replacement, and joint fusion, may be indicated in patients with RA to reduce pain and to improve function.
Carpal tunnel syndrome is common, and surgical repair may be curative if local injection therapy is unsuccessful.
Synovectomy may be helpful if major involvement is limited to one or two joints and if a 6-month trial of medical therapy has failed, but usually it is only of temporary benefit.
Prophylactic synovectomy and débridement of the ulnar styloid should be considered for patients with severe wrist disease to prevent rupture of the extensor tendons.
Other procedures that may be beneficial include total joint replacement of the hip and knee joints, resection of metatarsal heads in patients with bunion deformities, and subluxation of the toes. Reconstructive hand surgery may be useful in carefully selected patients.
Surgical fusion of joints usually results in freedom from pain but also in total loss of motion; this is tolerated well in the wrist and thumb.
Cervical spine fusion of C1 and C2 is indicated for significant cervical subluxation (>5 mm) with associated neurologic deficits.
Patients with RA undergoing elective surgical procedures should have a lateral cervical spine radiograph in flexion and extensions performed to screen for this subluxation.
Referrals
Rehabilitative therapy should be managed by a team of physicians, physical and occupational therapists, nurses, social workers, and psychologists. This approach may benefit patients with any form of arthritis.
Patient Education
Patient education, including pamphlets and support groups, is available in many communities through local chapters of the Arthritis Foundation.
Complications
Patients with RA and a single joint inflamed out of proportion to the rest of the joints must be evaluated for coexistent septic arthritis. This complication occurs with increased frequency in RA and carries a 20%÷30% mortality.
Osteoarthritis
General Principles
Definition
OA, or degenerative joint disease, is characterized by deterioration of articular cartilage, with subsequent formation of reactive new bone at the articular surface. The joints affected most commonly are the distal and proximal interphalangeal joints of the hands, hips, knees, and cervical and lumbar spine.
Epidemiology
The disease is more common in the elderly but may occur at any age, especially as a sequel to joint trauma, chronic inflammatory arthritis, or congenital malformation. OA of the spine may lead to spinal stenosis (neurogenic claudication), with aching or pain in the legs or buttocks on standing or walking.
Treatment
Medications
Acetaminophen in a dosage of up to 1,000 mg up to qid is the initial pharmacologic treatment.
Low-dose NSAIDs or selective COX-2 inhibitors are the next step, followed by full- dose treatment (see Therapeutic Approaches to Rheumatic Disease). However, because this patient population is often elderly and may have concomitant renal or cardiopulmonary disease, NSAIDs should be used with caution. NSAID-induced GI bleeding also is increased in the elderly population.
Glucosamine sulfate, 1,500 mg PO daily, may reduce symptoms as well as the rate of cartilage deterioration. Intra-articular glucocorticoid injections often are beneficial but probably should not be given more than every 3÷6 months (see Therapeutic Approaches to Rheumatic Disease).
Systemic steroids and narcotic analgesics should be avoided, although the µ-opioid agonist tramadol may be useful as an alternative analgesic agent.
Topical capsaicin may provide symptomatic relief with minimal toxicity.
Synthetic and naturally occurring hyaluronic acid derivatives (Hyalgan, Synvisc) can be administered intra-articularly. They reduce pain and improve mobility.
Surgery
When serious disability results from severe pain or deformity, surgery can be considered. Total hip or knee replacement usually relieves pain and increases function in selected patients.
Laminectomy and spinal fusion should be reserved for patients who have severe disease with intractable pain or neurologic complications. Lumbar spinal stenosis may require extensive decompressive laminectomy for relief of symptoms.
Nonoperative
Nonpharmacologic approaches may complement drug treatment of arthritis. Activities that involve excessive use of the joint should be identified and avoided. Brief periods of rest for the involved joint can relieve pain. Poor body mechanics should be corrected and malalignments such as pronated feet may be aided by orthotics. An exercise program to prevent or correct muscle atrophy can also provide pain relief. When weight-bearing joints are affected, support in the form of a cane, crutches, or a walker can be helpful, as well as weight reduction and wearing soft-soled shoes. Consultation with occupational and physical therapists may be helpful.
OA of the spine may cause radicular symptoms from pressure on nerve roots and often produces pain and spasm in the paraspinal soft tissues.
Physical supports (cervical collar, lumbar corset), local heat, and exercises to strengthen cervical, paravertebral, and abdominal muscles may provide relief in some patients.
Epidural steroid injections may reduce radicular symptoms.
Spondyloarthropathies
General Principles
Definition
The spondyloarthropathies are an interrelated group of disorders characterized by one or more of the following features: (a) spondylitis, (b) sacroiliitis, (c) enthesopathy (inflammation at sites of tendon insertion), and (d) asymmetric oligoarthritis. Extra-articular features of this group of disorders may include inflammatory eye disease, urethritis, and mucocutaneous lesions. The spondyloarthropathies aggregate in families, where they are associated with HLA-B27.
Ankylosing Spondylitis
Diagnosis
Clinical Presentation
Ankylosing spondylitis (AS) clinically presents as inflammation and ossification of the joints and ligaments of the spine and of the sacroiliac joints.
Hips and shoulders are the peripheral joints that are most commonly involved. Progressive fusion of the apophyseal joints of the spine occurs in many patients and cannot be predicted or prevented.
Treatment
Behavioral
Physical therapy emphasizing extension exercises and posture is recommended to minimize possible late postural defects and respiratory compromise.
Patients should be instructed to sleep supine on a firm bed without a pillow and to practice postural and deep-breathing exercises regularly.
Cigarette smoking should be discouraged strongly.
Medications
Nonsalicylate NSAIDs, such as indomethacin, are used to provide symptomatic relief, and selective COX-2 inhibitors are also effective (see Therapeutic Approaches to Rheumatic Disease).
Methotrexate and sulfasalazine provide benefit in some patients (see Therapeutic Approaches to Rheumatic Disease) (Table 23-1).
TNF blockade has been shown to be of benefit even in some patients with apparent fixed deformities.
Glucocorticoids and immunosuppressive therapy have been used occasionally in patients who do not respond to other agents.
Surgery
Many patients develop osteoporosis in the fused spondylitic spine and are at risk of spinal fracture. Surgical procedures to correct some spine and hip deformities may result in significant rehabilitation in carefully selected patients.
Referrals
Acute anterior uveitis occurs in up to 25% of patients with AS and should be managed by an ophthalmologist. Generally, this problem is self-limited, although glaucoma and blindness are unusual secondary complications.
Arthritis of Inflammatory Bowel Disease
General Principles
Arthritis of inflammatory bowel disease occurs in 10%÷20% of patients with Crohn's disease or ulcerative colitis and is similar to that of AS. It may also occur in some patients with intestinal bypass and diverticular disease.
Diagnosis
Clinical Presentation
Clinical features include spondylitis, sacroiliitis, and peripheral arthritis, particularly in the knee and ankle. Although peripheral joint disease may correlate with the activity of the colitis, spinal disease does not.
Diagnostic Procedures
Joint aspiration may be useful to exclude an associated septic arthritis, but antimicrobials are not effective in the management of sterile synovitis associated with colitis.
Treatment
Medications
As in AS, NSAIDs (other than salicylates) are the treatment of choice, and selective COX-2 inhibitors are also effective. However, GI intolerance of NSAIDs may be increased among this group of patients, and misoprostol may cause unacceptable diarrhea (see Therapeutic Approaches to Rheumatic Disease).
Sulfasalazine also may be beneficial for this form of arthritis (see Therapeutic Approaches to Rheumatic Disease) (Table 23-1).
Local injection of glucocorticoids and physical therapy are useful adjunctive measures.
Reiter Syndrome and Reactive Arthritis
General Principles
Epidemiology
Reiter syndrome is seen predominantly in young men and may occur with increased frequency in patients infected with HIV. Chlamydia infection has been implicated in some patients.
Etiology
A reactive arthritis may follow dysentery caused by Shigella flexneri, Salmonella species, Yersinia enterocolitica, or Clostridium difficile infections.
Diagnosis
Clinical Presentation
The clinical syndrome consists of asymmetric oligoarthritis, urethritis, conjunctivitis, and characteristic skin and mucous membrane lesions. The syndrome is usually transient, lasting from 1 to several months, but recurrences associated with varying degrees of disability are common.
Articular manifestations are identical to those of Reiter syndrome; extra-articular manifestations may occur but tend to be mild.
Treatment
Medications
Conservative therapy is indicated for control of pain and inflammation in these diseases.
Spontaneous remissions are common, making evaluation of therapy difficult.
NSAIDs (especially indomethacin) are often useful, and selective COX-2 inhibitors also provide relief (see Therapeutic Approaches to Rheumatic Disease).
Sulfasalazine or methotrexate may be of benefit in some patients (see Therapeutic Approaches to Rheumatic Disease) (Table 23-1).
In unusually severe cases, glucocorticoid therapy may be required to prevent rapid joint destruction (see Therapeutic Approaches to Rheumatic Disease) (Table 23-1).
Prolonged antibiotic therapy (such as doxycycline, 100 mg PO bid) may be beneficial in Reiter syndrome that is related to Chlamydia.
Referrals
Conjunctivitis usually is transient and benign, but ophthalmologic referral and treatment with topical or systemic glucocorticoids are indicated for iritis.
Psoriatic Arthritis
General Principles
Epidemiology
Seven percent of patients with psoriasis have some form of inflammatory arthritis.
Classification
Five major patterns of joint disease occur: (a) asymmetric oligoarticular arthritis, (b) distal interphalangeal joint involvement in association with nail disease, (c) symmetric rheumatoidlike polyarthritis, (d) spondylitis and sacroiliitis, and (e) arthritis mutilans.
Treatment
Medications
NSAIDs, particularly indomethacin, are used to treat the arthritic manifestations of psoriasis, in conjunction with appropriate measures for the skin disease.
Selective COX-2 inhibitors are also effective (see Therapeutic Approaches to Rheumatic Disease).
Intra-articular glucocorticoids may be useful in the oligoarticular form of the disease, but injection through a psoriatic plaque should be avoided. Severe skin and joint diseases generally respond well to methotrexate (see Therapeutic Approaches to Rheumatic Disease) (Table 23-1).
Sulfasalazine, leflunomide, TNF-α blockers, and hydroxychloroquine (see Therapeutic Approaches to Rheumatic Disease) (Table 23-1) may also have disease-modifying effects in polyarthritis.
Complications
When reconstructive joint surgery is performed, colonization of psoriatic skin with S. aureus increases the risk of wound infection.
Systemic Lupus Erythematosus
General Principles
Definition
SLE is a multisystem disease of unknown etiology that primarily affects women of childbearing age.
Pathophysiology
Autoantibodies to nuclear and other autoantigens are the hallmark of disease.
Diagnosis
Clinical Presentation
The course of this disease is highly variable and unpredictable.
Disease manifestations are protean, ranging in severity from fatigue, malaise, weight loss, arthritis or arthralgias, fever, photosensitivity, rashes, and serositis to potentially life-threatening thrombocytopenia, hemolytic anemia, nephritis, cerebritis, vasculitis, pneumonitis, myositis, and myocarditis.
Patients with lupus have accelerated coronary and peripheral vascular disease, which should be managed aggressively.
Treatment
Medications
NSAIDs usually control SLE-associated arthritis, arthralgias, fever, and serositis but not fatigue, malaise, or major organ system involvement. The response to selective COX-2 inhibitors is similar (see Therapeutic Approaches to Rheumatic Disease). Hepatic and renal toxicities of the NSAIDs appear to be increased in SLE. NSAIDs should be avoided in patients with active nephritis.
Hydroxychloroquine (see Therapeutic Approaches to Rheumatic Disease) (Table 23-1) may be effective in the treatment of rash, photosensitivity, arthralgias, arthritis, alopecia, and malaise associated with SLE and in the treatment of discoid and subacute cutaneous lupus erythematosus. Skin lesions may begin to improve within a few days, but joint symptoms may require 6÷10 weeks to subside. The drug is not effective for treating fever or renal, CNS, and hematologic problems.
Glucocorticoid therapy (see Therapeutic Approaches to Rheumatic Disease) (Table 23-1)
Indications for systemic glucocorticoids include (a) life-threatening manifestations of SLE, such as glomerulonephritis, CNS involvement, thrombocytopenia, and hemolytic anemia; and (b) debilitating manifestations of SLE (fatigue, rash) that are unresponsive to conservative therapy.
Dosage. Patients with severe or potentially life-threatening complications of SLE should be treated with prednisone, 1÷2 mg/kg PO daily, which can be given in divided doses. After disease is controlled, prednisone should be tapered slowly, the dosage being reduced by no more than 10% every 7÷10 days. More rapid reduction may result in relapse. Alternate-day therapy may reduce many of the adverse effects of long-term glucocorticoid therapy. IV pulse therapy in the form of methylprednisolone, 500 mg IV q12h for 3÷5 days, has been used in SLE in such life-threatening situations as rapidly progressive renal failure, active CNS disease, and severe thrombocytopenia. Patients who do not show improvement with this regimen probably are unresponsive to steroids, and other therapeutic alternatives must be considered. A course of oral prednisone should follow completion of pulse therapy. Electrolytes should be monitored in patients who receive high-dose steroids.
Immunosuppressive therapy (see Therapeutic Approaches to Rheumatic Disease) (Table 23-1)
Indications for immunosuppressive therapy in SLE include (a) such life-threatening manifestations of SLE as glomerulonephritis, CNS involvement, thrombocytopenia, and hemolytic anemia; and (b) the inability to reduce corticosteroid dosage or severe corticosteroid side effects.
Choice of an immunosuppressive is individualized to the clinical situation. Often, cyclophosphamide is used for life-threatening manifestations of SLE. High-dose IV pulse cyclophosphamide may be less toxic but also less immunosuppressive than is low-dose daily PO cyclophosphamide. Azathioprine and mycophenolate mofetil are used more often as steroid-sparing agents but may not be as effective as cyclophosphamide in treating nephritis. Rituximab, a monoclonal antibody directed against the B-cell surface molecule CD20, causes depletion of B cells and has been shown to be effective in cases of severe SLE not responding to conventional treatment.
Nonoperative
Conservative therapy is warranted if the patient's manifestations are mild.
General supportive measures include adequate sleep and avoidance of fatigue, as mild disease exacerbations may subside after a few days of bed rest.
For patients with photosensitive rashes, sunscreens with a sun protection factor of 30 or greater; protective clothing, such as a hat and long sleeves; and avoidance of sun exposure are recommended. Isolated skin lesions may respond to topical glucocorticoids.
Special Therapy
Transplantation and chronic hemodialysis have been used successfully in SLE patients with renal failure. Clinical and serologic evidence of disease activity often disappears
when renal failure ensues. The survival rate in these patients is equivalent to that of patients with other forms of chronic renal disease. Recurrence of nephritis in the allograft rarely occurs.
Special Considerations
Pregnancy in SLE. An increased incidence of second-trimester spontaneous abortion and stillbirth has been reported in some women with antibodies to cardiolipin or the lupus anticoagulant. Neonatal lupus may occur in offspring of anti-Ro/SSA positive mothers. SLE patients may experience an exacerbation in the activity of their disease in the third trimester or peripartum period. Differentiation between active SLE and pre-eclampsia often is difficult. Women whose SLE is in good control when they become pregnant are less likely to have a flare of disease during pregnancy.
Systemic Sclerosis
General Principles
Definition
Systemic sclerosis (scleroderma) is a systemic illness of unknown etiology characterized by thickening and hardening of the skin and visceral organs. Most of the manifestations of scleroderma have a vascular basis (Raynaud's phenomenon, telangiectasias, nailfold capillary changes, early edematous skin changes, nephrosclerosis), but frank vasculitis rarely is seen.
Classification
The label scleroderma includes diffuse scleroderma and limited scleroderma (formerly known as the CREST syndrome: calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias).
Diagnosis
Clinical Presentation
Diffuse scleroderma is characterized by extensive skin disease, the potential for hypertensive “renal crisis,” and shortened survival. Internal organs are affected.
GI involvement. Decreased motility of bowel segments can occur, leading to bacterial overgrowth, malabsorption, diarrhea, and weight loss.
Renal involvement. The appearance of hypertension and renal insufficiency, often associated with a microangiopathic hemolytic anemia, signals a poor prognosis.
Cardiopulmonary involvement. Patchy myocardial fibrosis can result in CHF or arrhythmias. Pulmonary involvement includes pleurisy with effusion, interstitial fibrosis, pulmonary hypertension, and cor pulmonale.
Limited scleroderma, in contrast, may be associated with primary pulmonary hypertension or biliary cirrhosis and has skin thickening that is limited to the face and the distal forearms and hands. GI involvement is seen.
Laboratory Studies
Up to 70% of patients with limited scleroderma have anticentromere antibody, which is not seen in individuals with diffuse scleroderma.
Treatment
Nonoperative
No curative therapy for scleroderma exists; instead, treatment focuses on particular organ involvement in a problem-oriented manner.
Skin and periarticular changes. No therapeutic agent is clearly effective for these cutaneous manifestations, although penicillamine or methotrexate is sometimes used. Physical therapy is important to retard and reduce joint contractures.
GI involvement
Reflux esophagitis generally responds to standard therapy (e.g., H2-receptor antagonists, proton pump inhibitors, and promotility agents.)
Treatment with broad-spectrum antimicrobials in a rotating sequence including metronidazole often improves the malabsorption. Metoclopramide may reduce bloating and distention.
Occasionally, esophageal strictures require mechanical esophageal dilation.
Rarely, severe constipation or intestinal pseudo-obstruction may occur.
Renal involvement. Aggressive blood pressure control with ACE inhibitors may delay or prevent the onset of uremia, particularly in patients with a serum creatinine of <3 mg/dL. Angiotensin-receptor blockade does not appear to be as effective.
Cardiopulmonary involvement. Coronary artery vasospasm can cause angina pectoris and may respond to calcium channel antagonists. Pulmonary involvement includes pleurisy with effusion, interstitial fibrosis, pulmonary hypertension, and cor pulmonale. Standard therapies for these conditions are used. Patients with rapidly progressive pulmonary parenchymal disease may benefit from a course of cyclophosphamide.
Raynaud's Phenomenon
General Principles
Definition
Raynaud's phenomenon is a reversible vasospasm of the digital arteries that can result in ischemia of the digits.
Treatment
Medications
Most pharmacologic approaches have had limited success.
Calcium channel antagonists (e.g., nifedipine) are the preferred initial agents, although they may exacerbate gastroesophageal reflux and constipation in these patients.
Alternative vasodilators, such as prazosin, occasionally are helpful, but significant side effects, especially orthostatic hypotension, may preclude their use.
Daily low-dose aspirin therapy is often prescribed for its antiplatelet effects.
Sympathetic ganglion blockade with a long-acting anesthetic agent may be useful when a patient has progressive digital ulceration that fails to improve with conservative therapy.
Surgery
Surgical digital sympathectomy may be beneficial.
Patient Education
Patients must be instructed to avoid exposure of the entire body to cold, protect the hands and feet from cold and trauma, and discontinue cigarette smoking.
Necrotizing Vasculitis
General Principles
Definition
Necrotizing vasculitis is characterized by inflammation and necrosis of blood vessels leading to tissue damage. This diagnosis includes a broad spectrum of disorders that have various causes and involve vessels of different types, sizes, and locations.
Pathophysiology
The immunopathogenic process often involves immune complexes.
Etiology
Although in most cases the inciting antigen has not been identified, vasculitic syndromes have been associated with chronic hepatitis B and C.
Diagnosis
Clinical Presentation
Table 23-2 summarizes clinical features and diagnostic and treatment approaches to the most common forms of vasculitis. Clinical features are diverse and depend in part on the size of the vessel involved. Systemic manifestations including fever and weight loss are also common. The response to therapy and the long-term prognosis of these disorders are highly variable.
Differential Diagnosis
Vasculitis “mimics” should be considered, including bacterial endocarditis, HIV, atrial myxoma, paraneoplastic syndromes, cholesterol emboli, and cocaine and amphetamine use.
Treatment
Medications
Glucocorticoids are the usual initial therapy and are beneficial in most vasculitides (see Therapeutic Approaches to Rheumatic Disease) (Table 23-1).
Although vasculitis that is limited to the skin may respond to lower doses of corticosteroids, the initial dosage for visceral involvement should be high (prednisone, 1÷2 mg/kg/d). If life-threatening manifestations are present, a brief course of high-dose pulse therapy with methylprednisolone, 500 mg IV q12h for 3÷5 days, should be considered.
Immunosuppressives, in particular oral cyclophosphamide, often are used in the initial management of necrotizing vasculitis, especially when major organ system involvement (e.g., lung, kidney, or nerve) is present (see Therapeutic Approaches to Rheumatic Disease) (Table 23-1).
TABLE 23-2 Clinical Features and Diagnostic and Treatment Approaches to Vasculitis
Vasculitic syndrome
Clinical features
Diagnostic approach
Treatment
Large-vessel involvement
Giant-cell arteritis
Headache
Temporal artery biopsy
Prednisone, 60÷80 mg/d
Jaw claudication
 
  Finger ischemia
Aortic arch arteriogram
Prednisone, 60÷80 mg/d
Arm claudication
 
 
Polyarteritis nodosa
Skin ulcers
Skin biopsy
Prednisone, 60÷100 mg/d
Cyclophosphamide, 1÷2 mg/kg/d, can be added
Nephritis
Renal biopsy
 
Mononeuritis multiplex
Sural nerve biopsy
Mesenteric ischemia
Mesenteric angiogram
Hepatitis B, C testing
  Sinusitis
c-ANCA
 
Pulmonary infiltrates
Nephritis
Lung biopsy
 
  Pulmonary infiltrates
p-ANCA
Prednisone, 60÷100 mg/d
Nephritis
Renal biopsy
Cyclophosphamide, 1÷2 mg/kg/d, can be added
  Skin ulcers
Skin or sural nerve biopsy
Prednisone, 60÷80 mg/d
Polyneuropathy
 
 
Cyclophosphamide, 1÷2 mg/kg/d, can be added
 
Hypersensitivity vasculitis
Palpable purpura
Skin biopsy
Prednisone, 20÷60 mg/d
 
Discontinue inciting drug
Henoch-Schönlein purpura
Palpable purpura
Skin biopsy
Supportive treatment
Nephritis
Renal biopsy
Prednisone, 20÷60 mg/d, may be needed
Mesenteric ischemia
 
 
 Trimethoprim/sulfamethoxazole can be used in variants of Wegener's granulomatosis limited to the upper airway and may also be useful in preventing relapse, but is not sufficient treatment for systemic disease. This drug is also used for P. carinii prophylaxis in patients who are receiving cyclophosphamide.
The use of biologic agents is under study and may provide further therapeutic options in the near future.
Referrals
Management should include consultation with a physician experienced in the treatment of these disorders. Treatment should be tailored to the severity of organ system in-volvement.
Polymyalgia Rheumatica and Temporal Arteritis
Diagnosis
Clinical Presentation
Polymyalgia rheumatica (PMR) presents in elderly patients as proximal limb girdle pain, morning stiffness, and constitutional symptoms.
Temporal arteritis (TA) is a form of vasculitis that presents with headache, scalp tenderness, jaw or tongue claudication, vision disturbances (including blindness), stroke, and, in up to 40% of patients, symptoms of PMR.
Laboratory Studies
PMR: elevated erythrocyte sedimentation rate (ESR)
TA: elevated ESR (often >100)
Surgical Diagnostic Procedures
The diagnosis of TA should be confirmed by temporal artery biopsy, which is not altered by 3÷5 days of prednisone therapy.
Treatment
Medications
PMR
If PMR is present without evidence of TA, prednisone, 10÷15 mg PO daily, usually produces dramatic clinical improvement within a few days.
The ESR should return to normal during initial treatment, but subsequent therapeutic decisions should be based on ESR and clinical status.
Glucocorticoid therapy can be tapered gradually to a maintenance dosage of 5÷10 mg PO daily but should be continued for at least 1 year to minimize the risk of relapse.
NSAIDs may facilitate reduction in prednisone dosage.
TA
Patients who are suspected of having TA should be treated promptly with prednisone, 1÷2 mg/kg/d PO daily, to prevent irreversible blindness.
High-dose steroid therapy should be continued until symptoms have abated and the ESR has returned to normal. The dosage then should be tapered gradually to 10÷20 mg, with close monitoring of the ESR and clinical status, and should be maintained for 1÷2 years.
Cryoglobulin Syndromes
General Principles
Definition
Cryoglobulins are serum proteins that reversibly precipitate in the cold.
Classification
Cryoglobulinemia is traditionally categorized as monoclonal (formerly type 1) or polyclonal (mixed; formerly types 2 and 3).
Etiology
Patients with monoclonal cryoglobulinemia usually have an underlying lymphoproliferative disorder such as myeloma or lymphoma.
The majority of patients with mixed cryoglobulinemia have hepatitis C; the remainder of cases are found in association with autoimmune disorders such as SLE or RA, or are idiopathic.
Diagnosis
Clinical Presentation
Symptoms are related to hyperviscosity (blurring of vision, digital ischemia, headache, lethargy) and respond to treatment of the underlying disorder, although plasmapheresis can be used in the acute setting.
Clinical manifestations of mixed cryoglobulinemia are mediated by immune complex deposition (arthralgias, purpura, glomerulonephritis, and neuropathy).
Treatment
Therapy for secondary cryoglobulinemic states is directed at the underlying disease.
Medication
Treatment of hepatitis C with interferon-α and ribavirin effectively reduces cryoglobulins, although they may recur when treatment is stopped.
Prednisone or immunosuppressive agents can be used to treat cryoglobulinemia due to SLE or RA but may exacerbate hepatitis C.
Polymyositis and Dermatomyositis
General Principles
Definition
Polymyositis (PM) is an inflammatory myopathy that presents as weakness and occasionally tenderness of the proximal musculature.
Dermatomyositis (DM) is PM with a concomitant rash.
Classification
PM÷DM can occur in three forms: (a) alone, (b) in association with any of the other autoimmune diseases, or (c) with a variety of neoplasms.
Diagnosis
Laboratory Studies
PM: elevated muscle enzyme levels (creatine kinase, aldolase, AST)
Certain subsets of disease are associated with myositis-specific antibodies such as Jo-1 and signal recognition particle. These antibodies have therapeutic and prognostic implications, and therefore levels should be measured in all patients.
Imaging
PM: abnormal electromyogram
Surgical Diagnostic Procedure
PM: muscle biopsy
Treatment
Medications
Prednisone
When PM÷DM occurs without associated disease, it usually responds well to prednisone, 1÷2 mg/kg PO daily (see Therapeutic Approaches to Rheumatic Disease) (Table 23-1).
Systemic complaints, such as fever and malaise, respond to therapy first, followed by muscle enzymes and, finally, muscle strength.
Once serum enzyme levels normalize, the prednisone dosage should be reduced slowly to maintenance levels of 10÷20 mg PO daily or 20÷40 mg PO every other day.
The appearance of steroid-induced myopathy and hypokalemia may complicate therapeutic assessment.
IV infusion of immunoglobulin may hasten improvement of severe dysphagia.
PM÷DM associated with neoplasia tends to be less responsive to glucocorticoid therapy but may improve after removal of an associated malignant tumor.
Patients who do not respond or cannot tolerate the side effects of glucocorticoids may respond to methotrexate or azathioprine (see Therapeutic Approaches to Rheumatic Disease) (Table 23-1).
The use of biologic agents is under study and may provide further therapeutic options in the near future.
Special Therapy
Physical therapy is essential in the management of myositis. Bed rest with active assisted range of motion is appropriate during very active disease, with more active exercise prescribed to improve strength once inflammation has been controlled.
Risk Management
Risk factors for malignancy in the setting of myositis include the presence of DM, cutaneous vasculitis, male sex, and advanced age.
Screening for common neoplasms, such as colon, lung, breast, and prostate cancer, should be considered in these patients.

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