10 December 2007

Reumatiod Arthritis

AUTHOR INFORMATION

Author: Randall W King, MD, Assistant Clinical Professor of Emergency Medicine, Medical College of Ohio; Program Director, Associate Chair, Department of Emergency Medicine, St Vincent Mercy Medical Center

Randall W King, MD, is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, National Association of EMS Physicians, Ohio State Medical Association, Society for Academic Emergency Medicine, and Wilderness Medical Society

Editor(s): Edward Bessman, MD, Chairman, Department of Emergency Medicine, John Hopkins Bayview Medical Center; Assistant Professor, Department of Emergency Medicine, Johns Hopkins University; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Gino A Farina, MD, Program Director, Associate Professor of Clinical Emergency Medicine, Department of Emergency Medicine, Long Island Jewish Medical Center, Albert Einstein College of Medicine; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Jonathan Adler, MD, Attending Physician, Department of Emergency Medicine, Massachusetts General Hospital; Division of Emergency Medicine, Harvard Medical School

 

INTRODUCTION

Background: Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease of undetermined etiology involving primarily the synovial membranes and articular structures of multiple joints. The disease is often progressive and results in pain, stiffness, and swelling of joints. In late stages deformity and ankylosis develop.

Pathophysiology: The cause of RA is unknown. The diagnosis is based routinely on the persistence of arthritic symptoms over time. The application of classification systems based on qualifying symptom criteria or on decision-tree methodology also aids in establishing a diagnosis.

Factors associated with RA include the possibility of infectious triggers, genetic predisposition, and autoimmune response. CD4+ T cells stimulate the immune cascade leading to cytokine production such as tumor necrosis factor alpha (TNF-a) and interleukin-1.

The primary targets of inflammation are synovial membranes and articular structures. Other organs are affected as well. Inflammation, proliferation, and degeneration typify synovial membrane involvement. Joint deformities and disability result from the erosion and destruction of synovial membranes and articular surfaces.

The disease course may be short and limited or progressive and severe.

Frequency:

  • In the US: Prevalence is approximately 1% in the United States. The occurrence rate ranges from 0.5% to greater than 5% depending on ethnic variation.
  • Internationally: Prevalence is similar to that in the United States.

Mortality/Morbidity: Mortality from RA is related primarily to the patient's overall deterioration in health, well-being, and functionality. Patients with RA become susceptible to infection and secondary organ dysfunction (eg, lung disease, kidney disease, GI hemorrhage).

Race: Rates for arthritis vary from approximately 5-6% in Asian/Pacific Islanders to 12% in African Americans and 16% in whites.

Sex: Female-to-male ratio is approximately 3:1.

Age: Age of onset is usually between 25 and 50 years. The disease can occur at any age but tends to peak in the fourth and fifth decades of life. The pediatric form of RA is juvenile rheumatoid arthritis (JRA), which is characterized by onset in children younger than 16 years and includes 3 categories of disease: polyarticular (ie, multiple joints affected), pauciarticular (ie, fewer than 4 joints affected), and systemic (ie, high fever, rash, organ involvement).

CLINICAL

History:

  • RA is usually a disease of insidious onset, although it can be abrupt. The diagnosis typically is made when 4 of 7 qualifying criteria established by the American Rheumatism Association are met. These qualifying criteria are as follows:
    • Morning stiffness lasting longer than 1 hour before improvement
    • Arthritis involving 3 or more joints
    • Arthritis of the hand, particularly involvement of the proximal interphalangeal (PIP) joints, metacarpophalangeal (MCP) joints, or wrist joints
    • Bilateral involvement of joint areas (ie, both wrists, symmetric PIP and MCP joints)
    • Positive serum rheumatoid factor (RF)
    • Rheumatoid nodules
    • Radiographic evidence of RA
  • Other contributing history includes the following:
    • General malaise
    • Weakness
    • Fever of undetermined etiology
    • Weight loss
    • Myalgias
    • Tendonitis
    • Bursitis

Physical:

  • Joint involvement is typically polyarticular and symmetrical, usually sparing the distal interphalangeal (DIP) joints. Joint involvement and inflammation is evinced by the following:
    • Edema
    • Effusion
    • Warmth
    • Tenderness to palpation
    • Destruction (a late finding)
    • Subcutaneous rheumatoid nodules, swan-neck deformities, boutonniere deformities, ulnar deviation of fingers at MCP joints (late findings)
    • Bursitis
  • Various inflammatory disorders of remote organ systems may be present and may contribute to the presenting problem. Organ systems that may be affected include the following:
    • Cardiac - Carditis, pericarditis
    • Pulmonary - Pleuritis, intrapulmonary nodules, interstitial fibrosis
    • Hepatic - Hepatitis
    • Ocular - Scleritis, episcleritis, dryness of the eyes
    • Vascular - Vasculitis
    • Skin - Subcutaneous nodules, ulcers
  • RA is a diffuse systemic disease involving many areas of the body. The presenting complaint may be remote from a joint or may involve inflammatory symptoms at a joint.

Causes:

  • The cause of RA has not been elucidated. Several possible associations have been described.
  • Associated factors may include the following:
    • Genetic predisposition
    • Female sex
    • Psychological stress
    • Immune response
    • Hormone interaction
    • Viral infection

DIFFERENTIALS

Cardiomyopathy, Dilated
Cardiomyopathy, Restrictive
Carpal Tunnel Syndrome
Cauda Equina Syndrome
Conjunctivitis
Corneal Ulceration and Ulcerative Keratitis
Costochondritis
Endocarditis
Gout and Pseudogout
Hepatitis
Inflammatory Bowel Disease
Iritis and Uveitis
Myocarditis
Myopathies
Pericarditis and Cardiac Tamponade
Polymyalgia Rheumatica
Polymyositis
Psoriasis
Reiter Syndrome
Sarcoidosis
Scleritis
Serum Sickness
Sjogren Syndrome
Systemic Lupus Erythematosus
Temporal Arteritis
Temporomandibular Joint Syndrome
Tendonitis
Tenosynovitis

Other Problems to be Considered:

Amyloidosis
Polyarteritis nodosa
Viral arthritis (eg, rubella, hepatitis B, parvovirus)
Whipple disease
Scleroderma
Paraneoplastic syndromes
Multicentric reticulohistiocytosis
Osteoarthritis (erosive)

WORKUP

Lab Studies:

  • Complete blood count (CBC) indicates the presence of anemia in approximately 80% of patients with RA. The anemia is normocytic and normochromic.
  • Thrombocytosis may be present.
  • Erythrocyte sedimentation rate (ESR) is elevated in approximately 90% of patients with RA. This test usually is not performed in the acute setting.
  • Serum RF result is positive in approximately 70% of patients with RA. This test is not routinely performed in the ED.
  • Antinuclear antibodies (ANA) are present in approximately 30% of patients with RA. This test is not routinely performed in the ED.

Imaging Studies:

  • Radiography
    • Joints: Typical findings occur later in the disease course and include bony erosions, cysts, osteopenia, joint space swelling, calcifications, narrowed joint space, deformities, separations, and fractures.
    • Cervical spine: RA can affect the cervical spine with inflammation and destruction of cartilage, bone, and ligaments. This most commonly occurs in the upper cervical spine. Laxity and destruction of ligaments can lead to significant instability with frank subluxation and cord damage.
  • CT and/or MRI of joints and cervical spine
    • CT and/or MRI can delineate further the pathology described above.
    • MRI may be necessary to demonstrate cord compression.

Other Tests:

  • Joint fluid analysis of an inflamed joint
    • Joint fluid analysis usually reveals a WBC count of 2,000-50,000/mm3 and no crystals or bacteria.
    • This may not be the case if gout, pseudogout, or infection is present.

Procedures:

  • Joint space aspiration
    • Consider joint space aspiration when making the definitive diagnosis of RA or when ruling out coexistent infection or crystal arthritis in an acutely swollen joint.
    • Analyze fluid for Gram stain, cell count, culture, and overall appearance.
    • Glucose and protein analyses are of limited value.

 

TREATMENT

Emergency Department Care: Many nonmedication therapies are available for RA, including exercise, diet, massage, counseling, stress reduction, physical therapy, and surgery. Medication-based therapies comprise several classes of drugs, including nonsteroidal anti-inflammatory drugs (NSAIDs), disease-modifying anti-rheumatologic drugs (DMARDs, also known as slow-acting antirheumatic drugs or SAARDS), immunosuppressants, biologic response modifiers, and corticosteroids. Although ED presentations may be due to initial disease presentation, patients with RA more commonly present with exacerbations of known disease or manifestations in other organ systems or sequelae. The following represent possible presentations:

  • Patients presenting with initial presentation of previously undiagnosed possible RA require symptomatic treatment with NSAID therapy and rapid referral for definitive diagnosis and institution of DMARD therapy. Delay of as little as 2-3 months in initiating joint sparing therapy results in significant irreversible joint damage measured radiographically at 5 years.
  • In patients with known disease, increased pain, edema, and dysfunction are characteristics of rheumatoid flare (exacerbation). Flares may be local or systemic in nature. Laboratory evaluation may reveal elevation in acute phase reactants. Treatment consists of rest, NSAIDs, DMARDs, short courses of steroids (2-4 wk), and possibly intraarticular steroid injections. Pain relief is important and may necessitate short-term use of narcotic analgesics.
  • Felty syndrome is a triad of RA, neutropenia, and splenomegaly. Patients with Felty syndrome are prone to serious bacterial infections that result in higher rates of morbidity and mortality than for other patients with RA. This requires prompt diagnosis and initiation of antibiotic therapy.
  • Ruptured Baker cysts are often confused with deep vein thrombosis (DVT). Baker cysts often occur fairly early in the course of the disease, with pain, edema, and inflammation in the posterior knee and calf. The diagnosis is best made with ultrasonography. Treatment includes rest, elevation, needle puncture of the calf, knee joint aspiration, and referral.
  • Carpal tunnel syndrome (median nerve compression neuropathy) is evinced by pain and/or paresthesias in the median nerve distribution of the hand, a positive Phalen and/or positive Tinel test, or positive electromyography. Therapy includes rest, temporary immobilization, NSAIDs, and surgery.
  • Cervical spine instability may be observed in patients with established RA who have degeneration of the ligaments and bone in the C-spine area. Degeneration of the transverse ligament can lead to instability at the C1-C2 level. Minor trauma can lead to neurologic sequelae due to inherent instability. Exercise caution when evaluating patients with RA after minor falls, motor vehicle accidents (MVAs), or other injuries. Cervical spine injury may occur spontaneously.
  • Keratoconjunctivitis sicca occurs in approximately 25% of patients with RA. Symptoms include ocular discharge, foreign body sensation, and dry eye. Episcleritis may progress to scleromalacia if untreated. Treatment includes referral to ophthalmology, artificial tears, systemic NSAIDs, topical NSAIDs, systemic steroids, and cyclophosphamide.
  • Patients with an established diagnosis of RA who are being treated with DMARDS, particularly those treated with combination therapy including the biologic response modifying agents such as anti-TNF antibody therapy, may be at an increased risk for serious infections and malignancies.

Consultations:

  • Consultation is necessary for this chronic disease. New onset disease requires rapid diagnosis and therapy with DMARDS. Rheumatoid flares and other sequelae require close follow up. Patients always should be referred back to their primary care physician/rheumatologist promptly for continuation of care.
  • Consultation with rheumatology, orthopedics, and/or infectious disease may be necessary if indicated by the presenting complaint.
  • Involvement by cardiology, pulmonology, nephrology, and ophthalmology often is necessitated by secondary organ involvement in those areas.

 

MEDICATION

The treatment of RA historically has been a stepwise, pyramid progression beginning with rest, salicylates, and NSAIDs and progressing to the use of disease-modifying medications. Current recommendations suggest that for all but minor disease, the use of DMARDs and biologic response modifiers or combination drug therapy earlier in the disease course is more effective. Destruction of synovial tissue and joints can occur early in the disease process, before patients classically have been considered for progression of therapy.

Effective medications include methotrexate, sulfasalazine, corticosteroids, hydroxychloroquine, gold injections, d-penicillamine, minocycline, azathioprine, cyclosporine, etanercept, leflunomide, infliximab, adalimumab, etanercept, abatacept, and anakinra. The primary goals of ED management should be relief of acute symptomatology, ruling out significant complications, and coordination of chronic therapy with the patient's primary care physician and rheumatologist.

Drug Category: Nonsteroidal anti-inflammatory drugs (NSAIDs) -- NSAIDs have been the cornerstone of therapy for RA. NSAIDs reduce pain and inflammation and allow for improvements in mobility and function. Several NSAIDs exist, but no single agent is clearly superior to another. The cyclooxygenase-2 (COX-2) inhibitors may offer some increase in efficacy with fewer adverse GI effects. The use of NSAIDs alone as single agents in RA should be reserved for mild, well-controlled disease. COX-2 inhibitors may be more effective in controlling inflammation.

Drug Name
Ibuprofen (Ibuprin, Advil, Motrin) -- Available OTC and as prescription. Acts by blocking prostaglandin and thereby decreasing vessel dilatation and inflammation.

Adult Dose
200-800 mg PO q6h

Pediatric Dose
5-10 mg/kg PO q6h

Contraindications
Documented hypersensitivity, peptic ulcer disease, recent GI bleeding or perforation, renal insufficiency, or high risk of bleeding

Interactions
Aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity; may decrease effects of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; monitor PT closely (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; may increase phenytoin levels

Pregnancy
D - Unsafe in pregnancy

Precautions
Caution in congestive heart failure, hypertension, and decreased renal and hepatic function; caution in anticoagulation abnormalities or during anticoagulant therapy

Drug Category: Cyclooxygenase-2 (COX-2) inhibitors -- Although increased cost can be a negative factor, the incidence of costly and potentially fatal GI bleeds is possibly less with COX-2 inhibitors than with traditional NSAIDs. Ongoing analysis of cost avoidance of GI bleeds will further define the populations that will find COX-2 inhibitors the most beneficial.

Drug Name
Celecoxib (Celebrex) -- Has anti-inflammatory, analgesic, and antipyretic activity. Blocks prostaglandin synthesis by inhibiting COX-2 while leaving COX-1 unaffected.

Adult Dose
100-200 mg PO bid

Pediatric Dose
Not established

Contraindications
Documented hypersensitivity, hypersensitivity to aspirin or sulfa drugs, asthma induced by NSAID or aspirin

Interactions
May decrease effectiveness and increase renal toxicity of ACE inhibitors; may reduce effectiveness of angiotensin II blockers; may increase risk of GI bleeding with aspirin; may induce sodium/water retention and decrease effectiveness of oral beta-blockers; may increase sodium/water retention and GI bleeding due to corticosteroids; may decrease effectiveness of diuretics; fluconazole may increase levels; may increase levels of lithium, methotrexate, other NSAIDs, and warfarin

Pregnancy
C - Safety for use during pregnancy has not been established.

Precautions
May cause fluid retention and peripheral edema; caution in compromised cardiac function, hypertension, conditions predisposing to fluid retention, severe heart failure, and hyponatremia because may deteriorate circulatory hemodynamics; NSAIDs may mask usual signs of infection; caution in presence of existing controlled infections; evaluate symptoms and signs suggesting liver dysfunction or abnormal LFT results

Drug Category: Disease-modifying agents -- These drugs most frequently are used in various combination therapy regimens. They include methotrexate, hydroxychloroquine, gold, d-penicillamine, sulfasalazine, cyclosporine A, minocycline, azathioprine, leflunomide, infliximab, and etanercept. Please note that in JRA, d-penicillamine, gold, and antimalarials have not been proven effective. Pediatric safety has not been established for some of the newer agents.

Drug Name
Methotrexate (Rheumatrex) -- An important agent in control of RA. Antimetabolite that has various immunologic effects. Actual mechanism with RA is unknown.

Adult Dose
0.2-0.4 mg/kg PO each wk as single dose

Pediatric Dose
0.2-0.4 mg/kg PO each wk as single dose
10-15 mg/m2/wk PO each wk, divided qd, or in 3 divided doses

Contraindications
Documented hypersensitivity, alcoholism, hepatic insufficiency, documented immunodeficiency syndromes, preexisting blood dyscrasias (eg, bone marrow hypoplasia, leukopenia, thrombocytopenia, significant anemia)

Interactions
Coadministration with NSAIDs may be fatal; oral aminoglycosides may decrease absorption and blood levels; charcoal lowers levels; concurrent etretinate may increase hepatotoxicity; folic acid or its derivatives contained in some vitamins may decrease response; indomethacin and phenylbutazone can increase plasma levels; may decrease phenytoin serum levels; probenecid, salicylates, procarbazine, and sulfonamides, including TMP-SMZ, may increase effects and toxicity; may increase plasma levels of thiopurines

Pregnancy
X - Contraindicated in pregnancy

Precautions
Monitor CBCs monthly and liver and renal functions q1-3mo during therapy (monitor more frequently during initial dosing, dose adjustments, or when risk of elevated methotrexate levels, eg, dehydration); has toxic effects on hematologic, renal, GI, pulmonary, and neurologic systems; discontinue if significant drop in blood counts; aspirin, NSAIDs, or low-dose steroids may be administered concomitantly (possibility of increased toxicity with NSAIDs, including salicylates, has not been tested)

Drug Name
Leflunomide (Arava) -- An immune response-modifying agent that inhibits T-cell proliferation and reduces inflammation.

Adult Dose
100 mg PO qd for 3 d, initially, followed by a maintenance dose of 10-20 mg PO qd

Pediatric Dose
Not established

Contraindications
Documented hypersensitivity

Interactions
Cholestyramine and charcoal reduce effects; concomitant administration with rifampin increases toxicity

Pregnancy
X - Contraindicated in pregnancy

Precautions
Serious adverse reactions include hepatotoxicity and immunosuppression; other reactions include nausea, diarrhea, abdominal pain, rash, bronchitis, headache, hypertension, dizziness, and alopecia; caution if impaired liver or renal function or if immunodeficient

Drug Name
Azathioprine (Imuran) -- Antagonizes purine metabolism and inhibits synthesis of DNA, RNA, and proteins. May decrease proliferation of immune cells, which results in lower autoimmune activity.

Adult Dose
1 mg/kg/d PO for 6-8 wk; increase by 0.5 mg/kg q4wk until response or dose reaches 2.5 mg/kg/d

Pediatric Dose
Not established

Contraindications
Documented hypersensitivity; low levels of serum thiopurine methyl transferase (TPMT)

Interactions
Toxicity increases with allopurinol; concurrent use with ACE inhibitors may induce severe leukopenia; may increase levels of methotrexate metabolites and decrease effects of anticoagulants, neuromuscular blockers, and cyclosporine

Pregnancy
D - Unsafe in pregnancy

Precautions
Increases risk of neoplasia; caution with liver disease and renal impairment; hematologic toxicities may occur; check TPMT level before therapy and follow liver, renal, and hematologic function; pancreatitis rarely associated

Drug Name
Sulfasalazine (Azulfidine EN-tabs) -- Decreases the inflammatory response and systemically inhibits prostaglandin synthesis.

Adult Dose
0.5-1g/d PO; increase qwk to maintenance dose of 2 g/d PO divided bid; increase to 3 g/d if response not satisfactory after 12 wk of treatment; not to exceed 3 g/d

Pediatric Dose
Not established

Contraindications
Documented hypersensitivity; sulfa drugs or any component and those diagnosed with GI or GU obstruction

Interactions
Decreases effects of iron, digoxin, and folic acid; conversely, increases effect of oral anticoagulants, oral hypoglycemic agents, and methotrexate

Pregnancy
B - Usually safe but benefits must outweigh the risks.

Precautions
Caution in patients with renal or hepatic impairment, blood dyscrasias, or urinary obstruction

Drug Name
Infliximab (Remicade) -- Chimeric IgG1k monoclonal antibody that neutralizes cytokine TNF-a and inhibits its binding to TNF-a receptor. Reduces infiltration of inflammatory cells and TNF-a production in inflamed areas. Used with methotrexate in patients who have had inadequate response to methotrexate monotherapy.

Adult Dose
3 mg/kg IV (in combination with methotrexate therapy); follow by additional 3 mg/kg at 2wk and 6 wk after first dose; repeat q8wk thereafter

Pediatric Dose
Not established

Contraindications
Documented hypersensitivity to murine proteins or components of formulation; serious clinical infections

Interactions
None reported

Pregnancy
B - Usually safe but benefits must outweigh the risks.

Precautions
TNF alpha modulates cellular immune responses; anti-TNF therapies, such as infliximab, may adversely affect normal immune responses and allow development of superinfections; may increase risk of reactivation of tuberculosis in patients with particular granulomatous infections

Drug Name
Adalimumab (Humira) -- Recombinant human IgG1 monoclonal antibody specific for human tumor necrosis factor (TNF). Indicated to reduce inflammation and inhibit progression of structural damage in moderate-to-severe rheumatoid arthritis. Reserved for those who experience inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs). Can be used alone or in combination with MTX or other DMARDs. Binds specifically to TNF-alpha and blocks interaction with p55 and p75 cell-surface TNF receptors.

Adult Dose
40 mg SC q2wk; may increase to 40 mg SC qwk in some patients not taking concomitant MTX

Pediatric Dose
Not established

Contraindications
Documented hypersensitivity; active infection

Interactions
May interfere with immune response to live-virus vaccine (MMR) and reduce efficacy; MTX decreases clearance (available data do not support adjusting dose of either Humira or MTX)

Pregnancy
B - Usually safe but benefits must outweigh the risks.

Precautions
Causes immunosuppression; may reactivate tuberculosis infection; increases risk for lymphoma development; associated with CNS demyelination (rare); discontinue if serious infection develops; autoantibody development may occur causing lupuslike syndrome

Drug Name
Etanercept (Enbrel) -- Acts by binding and inhibiting TNF, cytokine that contributes to inflammatory and immune response.

Adult Dose
25 mg SC twice/wk

Pediatric Dose
0.4 mg/kg SC; not to exceed 25 mg/dose

Contraindications
Documented hypersensitivity, sepsis, concurrent live vaccination

Interactions
None reported

Pregnancy
B - Usually safe but benefits must outweigh the risks.

Precautions
Caution in impaired renal function and asthma; discontinue administration if a serious infection develops; adverse effects may include injection site pain, localized erythema, rash, URI symptomatology, GI upset, nausea, vomiting, rhinitis, and cough

Drug Category: Immunomodulators -- Interfere with cytokine actions responsible for inflammation.

Drug Name
Abatacept (Orencia) -- Selective co-stimulation modulator that inhibits T-cell activation by binding to CD80 and CED86, thereby blocking CD28 interaction. CD28 interaction provides a signal needed for full T-cell activation that is implicated in RA pathogenesis. Indicated for reducing signs and symptoms of RA, slowing progression of structural damage and improving physical function in adults with moderate-to-severe RA who have inadequate response to DMARDs, methotrexate, or TNF antagonists. May be used as monotherapy or with DMARDs (other than TNF antagonists, because of increased risk of serious infections [4.4% vs 0.8%]). Not recommended for concomitant use with anakinra (insufficient experience).

Adult Dose
Dose according to body weight; after initial administration, repeat at 2 and 4 wk after first infusion, then q4wk; infuse over 30 min
<60 kg: 500 mg IV
60-100 kg: 750 mg IV
>100 kg: 1 g IV

Pediatric Dose
Not established

Contraindications
Documented hypersensitivity

Interactions
In clinical trials, coadministration with TNF antagonists resulted in increased risk of serious infections; do not administer concurrently with live-virus vaccines (eg, MMR) or within 3 mo of discontinuation

Pregnancy
C - Safety for use during pregnancy has not been established.

Precautions
Discontinue if serious infection occurs; patients with COPD developed adverse effects more frequently, including COPD exacerbations, cough, rhonchi, and dyspnea; serious adverse reactions include serious infections (3% vs 1.9% placebo); malignancy frequency was similar to that of placebo (1.3% vs 1.1% placebo), with the exception of lung cancer (0.2% vs 0% placebo); common adverse effects include headache, upper respiratory tract infection, nasopharyngitis, and nausea

Drug Category: Interleukin-1 receptor inhibitors -- Block effects of interleukin-1, which, in turn, may reduce inflammation and pain.

Drug Name
Anakinra (Kineret) -- Competitively and selectively inhibits interleukin-1 (IL-1) binding to type I receptor (IL-1RI). IL-1 is found in excess in rheumatoid arthritis patients and is produced in response to inflammatory stimuli. By blocking IL-1 binding, inflammation and pain associated with rheumatoid arthritis are inhibited. Indicated for rheumatoid arthritis in patients who have failed one or more disease-modifying antirheumatic drugs (DMARDS). Dose should be administered at approximately the same time every day.

Adult Dose
100 mg SC qd

Pediatric Dose
Not established

Contraindications
Documented hypersensitivity to product or E coli-derived products; active infections

Interactions
None reported; higher rate of serious infections and neutropenia are possible when coadministered with TNF blocking agents (eg, etanercept, infliximab); may decrease response to live virus vaccines

Pregnancy
B - Usually safe but benefits must outweigh the risks.

Precautions
Serious infections may occur (discontinue treatment if serious infection develops); neutropenia may occur (especially if administered concomitantly with TNF blocking agents); most common adverse effect is local reaction at site of injection; caution if administered to nursing women

Drug Category: Glucocorticoids -- These agents, used alone or in conjunction with other medications, may reduce the symptomatology associated with RA. These drugs can be given at low doses daily for maintenance or in large doses pulsed over 3 days for a rheumatoid flare.

Drug Name
Prednisone (Deltasone, Orasone, Sterapred) -- Used as an immunosuppressant in treatment of autoimmune disorders. By reversing increased capillary permeability and suppressing PMN activity, may decrease inflammation.
Should be given in as low a dose as possible. Long-term administration of more than 8-10 mg/d may cause significant adverse effects. Strongly recommend avoiding in children unless other agents are unsuccessful.

Adult Dose
Maintenance: 5-10 mg PO qd
Flare: 20-50 mg PO qd for 1-3 doses

Pediatric Dose
Maintenance: 0.1 mg/kg/d PO
Flare: 2-5 mg/kg/d PO for 1-3 d

Contraindications
Documented hypersensitivity, viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, fungal or tubercular skin infections, GI ulceration

Interactions
Estrogens may decrease clearance; concurrent digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Pregnancy
B - Usually safe but benefits must outweigh the risks.

Precautions
Avoid in children unless other agents ineffective; abrupt discontinuation of glucocorticoids may cause adrenal crisis; other adverse effects may include hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections

 

FOLLOW-UP

Deterrence/Prevention:

  • As the cause of RA is unknown, methods of preventing the disease have not been established.
  • Many approaches have been suggested to prevent or minimize recurrences or flares. These include proper nutrition, relaxation, low-impact exercise, flexibility exercises, yoga, tai chi, counseling, meditation, hydrotherapy, and stress reduction.

Prognosis:

  • Prognosis in RA is extremely variable.
  • Some evidence suggests that the onset of disease (rapid versus insidious) may predict the progression of disease. Patients with rapid onset of disease may show better remission than those with insidious onset.
  • Prognosis is worse with large joint involvement.

Patient Education:

  • Patients with RA require a great deal of education regarding the need for lifestyle changes to prevent exacerbations, to preserve mobility and functionality, and for appropriate pain management. Specific education for the ED visit is focused on the exacerbation or focal problem for which the patient presents.

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  • Reference Link:

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    1 comment:

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